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CAMIP causal chains
CAMIP stands for Causal Analysis of Mechanistic Inference in Pharmacogenomics. Each Tier 1 record links a receptor-peak-associated pharmacogene to an inducer and relevant drug associations through a reviewed mechanistic chain. Drug context is informed by PharmGKB clinical annotations and the cited literature. These receptors govern the inducible enzymes and transporters that handle a large share of clinically used drugs and their interactions. The CYP3A subfamily alone metabolizes roughly 30% of marketed drugs, as summarized in a CYP450 metabolism review, and the panel further spans CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, UGT1A1 and major hepatic transporters, covering many first line agents prone to drug interactions driven by induction. CAMIP describes mechanism only and gives no dosing, monitoring, severity, or treatment recommendations.
Submitted pharmacist decisions, revisions and notes are shown below verbatim, in their original language. A submitted review is not necessarily an approval: the decision is retained exactly as entered. Prior explanatory context is available separately and is not the pharmacist's submitted wording; the submitted review takes precedence.
Tier 1: peak-anchored panel (29 reviewed records)
FXR axis
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Reduced FXR/RXRα binding impairs receptor-mediated transactivation of ABCB11, reducing BSEP expression and thereby limiting adaptive increases in canalicular ATP-dependent bile salt export. Under increased bile salt load, this impaired inducibility may promote intracellular bile salt accumulation and increase susceptibility to drug-induced cholestatic liver injury.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- overlapping TSS
- Predicted consequence
- Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, abolishing the critical canalicular expression of the Bile Salt Export Pump. This directly cripples the ATP-dependent rate-limiting step of hepatic bile acid elimination, precipitating toxic intracellular bile salt accumulation and rendering hepatocytes profoundly vulnerable to severe drug-induced cholestatic liver injury under medications such as bosentan and cyclosporine.
- Prior narrative
- Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, abolishing the critical canalicular expression of the Bile Salt Export Pump. This directly cripples the ATP-dependent rate-limiting step of hepatic bile acid elimination, precipitating toxic intracellular bile salt accumulation and rendering hepatocytes profoundly vulnerable to severe drug-induced cholestatic liver injury under medications such as bosentan and cyclosporine.
- Drug context
- bosentan; cyclosporine; estrogens
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of ABCB4 expression may limit adaptive increases in ATP-dependent phospholipid translocation across the canalicular membrane of hepatocytes, reducing biliary phospholipid secretion and phospholipid-dependent buffering of bile salts.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- at promoter -6485 bp
- Predicted consequence
- Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, impairing the coordinated up-regulation of ABCB4. This leads to a deficiency in ATP-dependent phospholipid translocation across the canalicular membrane of hepatocytes, decreasing biliary phospholipid secretion and increasing the physiological susceptibility to intrahepatic cholestasis and gallstone formation.
- Prior narrative
- Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, impairing the coordinated up-regulation of ABCB4. This leads to a deficiency in ATP-dependent phospholipid translocation across the canalicular membrane of hepatocytes, decreasing biliary phospholipid secretion and increasing the physiological susceptibility to intrahepatic cholestasis and gallstone formation.
- Drug context
- imatinib; anthracyclines and related substances
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- in distal enhancer +19834 bp
- Predicted consequence
- Altered receptor-mediated feedback repression of CYP8B1, shifting the cholic acid to chenodeoxycholic acid synthesis ratio in endogenous bile acid pathways.
- Prior narrative
- Altered receptor-mediated feedback repression of CYP8B1, shifting the cholic acid to chenodeoxycholic acid synthesis ratio in endogenous bile acid pathways.
- Drug context
- none in routine clinical use, endogenous or bile acid pathway
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of intestinal FGF19 expression may weaken gut–liver endocrine signaling, thereby attenuating feedback repression of hepatic bile acid biosynthesis.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- at promoter -2789 bp
- Predicted consequence
- Attenuated receptor-mediated transcriptional activation of enterocyte FGF19, disrupting the intestinal endocrine signaling cascade required for the downstream feedback repression of hepatic bile acid biosynthesis.
- Prior narrative
- Attenuated receptor-mediated transcriptional activation of enterocyte FGF19, disrupting the intestinal endocrine signaling cascade required for the downstream feedback repression of hepatic bile acid biosynthesis.
- Drug context
- none in routine clinical use, endogenous or bile acid pathway
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- overlapping TSS
- Predicted consequence
- Blunted receptor-mediated induction of NR0B2 expression, weakening the downstream transcriptional feedback inhibition of hepatic bile acid synthesis pathways.
- Prior narrative
- Blunted receptor-mediated induction of NR0B2 expression, weakening the downstream transcriptional feedback inhibition of hepatic bile acid synthesis pathways.
- Drug context
- none in routine clinical use, endogenous or bile acid pathway
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Reduced FXR binding would weaken FXR-driven SHP induction; with SHP-mediated repression relieved, SLC10A1/NTCP expression would rise, thus increasing the hepatic clearance of NTCP substrates.
Reviewer notes (verbatim)
Rosuvastatin 不在 PharmGKB 臨床註釋
Polymorphisms in SLC10A1 had minimal effects on the plasma concentration of rosuvastatin in Chinese patients with hypercholesterolemia (PMID: 23930675).
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- in distal enhancer +11900 bp
- Predicted consequence
- Reduced FXR binding would weaken FXR-driven SHP induction; with SHP-mediated repression relieved, SLC10A1/NTCP expression would rise, thus increasing the hepatic clearance of NTCP substrates.
- Prior narrative
- Reduced FXR binding would weaken FXR-driven SHP induction; with SHP-mediated repression relieved, SLC10A1/NTCP expression would rise, thus increasing the hepatic clearance of NTCP substrates.
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of SLC51A expression may impair bile salt export from enterocytes and the inducible basolateral bile salt efflux route in hepatocytes under increased intracellular bile salt load.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- at promoter +1088 bp
- Predicted consequence
- Blunted receptor-mediated induction of SLC51A expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes.
- Prior narrative
- Blunted receptor-mediated induction of SLC51A expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes.
- Drug context
- none in routine clinical use, endogenous or bile acid pathway
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of SLC51B expression may impair bile salt export from enterocytes and the inducible basolateral bile salt efflux route in hepatocytes under increased intracellular bile salt load.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Obeticholic acid; Experimental GW4064
- Regulatory element
- overlapping TSS
- Predicted consequence
- Blunted receptor-mediated induction of SLC51B expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes.
- Prior narrative
- Blunted receptor-mediated induction of SLC51B expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes.
- Drug context
- none in routine clinical use, endogenous or bile acid pathway
PXR axis
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated induction of ABCC2 may attenuate inducible canalicular efflux of its substrates, including conjugated metabolites, into bile.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -440 bp
- Predicted consequence
- Blunted receptor-mediated induction of ABCC2 expression, diminishing canalicular efflux capacity and reducing the clearance of clearance-dependent substrates.
- Prior narrative
- Blunted receptor-mediated induction of ABCC2 expression, diminishing canalicular efflux capacity and reducing the clearance of clearance-dependent substrates.
- Drug context
- tenofovir; methotrexate; mycophenolic acid; talinolol; lopinavir; tacrolimus
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -544 bp
- Predicted consequence
- Blunted receptor-mediated induction of ABCC3 expression, weakening basolateral transport capacity for organic anions and drug conjugates such as methotrexate and morphine-glucuronide.
- Prior narrative
- Blunted receptor-mediated induction of ABCC3 expression, weakening basolateral transport capacity for organic anions and drug conjugates such as methotrexate and morphine-glucuronide.
- Drug context
- cisplatin; morphine; cyclophosphamide; doxorubicin; methotrexate; vincristine
Submitted decision (verbatim): 接受
Reviewer notes (verbatim)
Blunted PXR-mediated induction of CES2 may attenuate inducible prodrug bioactivation, including the hydrolysis of irinotecan to SN-38.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -111 bp
- Predicted consequence
- Blunted receptor-mediated induction of CES2 expression, impairing the hydrolytic bioactivation of key prodrugs such as irinotecan.
- Prior narrative
- Blunted receptor-mediated induction of CES2 expression, impairing the hydrolytic bioactivation of key prodrugs such as irinotecan.
- Drug context
- irinotecan
Submitted decision (verbatim): 接受
Reviewer notes (verbatim)
Blunted receptor-mediated induction of CYP2A6 decreases the hepatic oxidative metabolism and clearance of its substrates such as nicotine and coumarin.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- in distal enhancer +21719 bp
- Predicted consequence
- Blunted receptor-mediated induction of CYP2A6 decreases the hepatic oxidative metabolism and clearance of its substrates such as nicotine and coumarin.
- Prior narrative
- Blunted receptor-mediated induction of CYP2A6 decreases the hepatic oxidative metabolism and clearance of its substrates such as nicotine and coumarin.
- Drug context
- nicotine; coumarin; tegafur; efavirenz; letrozole; metronidazole
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of CYP2C19 lowers antiplatelet effect of the prodrug clopidogrel, and raises exposure of voriconazole.
Reviewer notes (verbatim)
參考文獻目前沒有提到 clopidogrel 和 voriconazole 的藥理與藥物動力學，可以考慮補充 PMID 38899464 & PMID 27981572
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- in distal enhancer +14490 bp
- Predicted consequence
- Blunted receptor-mediated induction of CYP2C19 lowers antiplatelet effect of the prodrug clopidogrel, and raises exposure of voriconazole.
- Prior narrative
- Blunted receptor-mediated induction of CYP2C19 lowers antiplatelet effect of the prodrug clopidogrel, and raises exposure of voriconazole.
- Drug context
- clopidogrel; voriconazole; omeprazole; lansoprazole; citalopram; escitalopram
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of CYP2C8 reduces the inducible metabolic clearance of substrates such as repaglinide and paclitaxel.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -1846 bp
- Predicted consequence
- Blunted receptor-mediated induction of CYP2C8 reduces the inducible metabolic clearance of substrates such as repaglinide and paclitaxel.
- Prior narrative
- Blunted receptor-mediated induction of CYP2C8 reduces the inducible metabolic clearance of substrates such as repaglinide and paclitaxel.
- Drug context
- ibuprofen; tacrolimus; rosiglitazone; pioglitazone; amodiaquine; paclitaxel
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of CYP2C9 reduces the inducible metabolism of narrow-therapeutic-index substrates such as warfarin and phenytoin.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -1557 bp
- Predicted consequence
- Blunted receptor-mediated induction of CYP2C9 reduces the inducible metabolism of narrow-therapeutic-index substrates such as warfarin and phenytoin.
- Prior narrative
- Blunted receptor-mediated induction of CYP2C9 reduces the inducible metabolism of narrow-therapeutic-index substrates such as warfarin and phenytoin.
- Drug context
- warfarin; phenytoin; celecoxib; fluvastatin; ibuprofen; meloxicam
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
CYP3A subfamily enzymes metabolize ~30% of clinically used drugs. Blunted receptor-mediated induction of CYP3A4 reduces its inducible metabolic capacity under PXR inducers.
Reviewer notes (verbatim)
參考文獻 2 建議改為 PMID 23333322，CYP3A4 所代謝的臨床用藥比例較無定論。
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -137 bp
- Predicted consequence
- CYP3A subfamily enzymes metabolize ~30% of clinically used drugs. Blunted receptor-mediated induction of CYP3A4 reduces its inducible metabolic capacity under PXR inducers.
- Prior narrative
- CYP3A subfamily enzymes metabolize ~30% of clinically used drugs. Blunted receptor-mediated induction of CYP3A4 reduces its inducible metabolic capacity under PXR inducers.
- Drug context
- quetiapine; tacrolimus; fentanyl; cyclosporine; sufentanil; simvastatin
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- overlapping TSS
- Predicted consequence
- Blunted receptor-mediated induction of CYP3A5, reducing the inducible component of metabolic clearance specifically in CYP3A5-expressing individuals.
- Prior narrative
- Blunted receptor-mediated induction of CYP3A5, reducing the inducible component of metabolic clearance specifically in CYP3A5-expressing individuals.
- Drug context
- tacrolimus; cyclosporine; everolimus; sirolimus; fentanyl; carbamazepine
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated induction of CYP3A7 may reduce inducible CYP3A7-mediated xenobiotic metabolism, particularly during fetal and perinatal development.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -7497 bp
- Predicted consequence
- Blunted receptor-mediated induction of CYP3A7, attenuating inducible developmental xenobiotic detoxification pathways.
- Prior narrative
- Blunted receptor-mediated induction of CYP3A7, attenuating inducible developmental xenobiotic detoxification pathways.
- Drug context
- tacrolimus
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated induction of SULT2A1 may attenuate inducible sulfonation of hydroxysteroids and other SULT2A1 substrates.
Reviewer notes (verbatim)
DHEA; budesonide 不在 PharmGKB 臨床註釋
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -63 bp
- Predicted consequence
- Blunted receptor-mediated induction of SULT2A1, reducing the inducible sulfonation capacity for hydroxysteroids and clinical substrates such as budesonide.
- Prior narrative
- Blunted receptor-mediated induction of SULT2A1, reducing the inducible sulfonation capacity for hydroxysteroids and clinical substrates such as budesonide.
- Drug context
- DHEA; budesonide
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted receptor-mediated induction of UGT1A1, reducing the inducible glucuronidation capacity. For irinotecan, reduced glucuronidation of the active metabolite SN-38 may increase toxicity.
Reviewer notes (verbatim)
Atazanavir & irinotecan 是經典的 UGT1A1 相關藥物，如果需要補充可以參考 PMID 26417955 & PMID 17728214
Atazanavir 是 UGT1A1 抑制劑，非受質
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -137 bp
- Predicted consequence
- Blunted receptor-mediated induction of UGT1A1, reducing the inducible glucuronidation capacity. For irinotecan, reduced glucuronidation of the active metabolite SN-38 may increase toxicity.
- Prior narrative
- Blunted receptor-mediated induction of UGT1A1, reducing the inducible glucuronidation capacity. For irinotecan, reduced glucuronidation of the active metabolite SN-38 may increase toxicity.
- Drug context
- irinotecan/SN-38 (SN-38 substrate pathway); atazanavir (UGT1A1 inhibitor)
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated induction of UGT1A3 may attenuate inducible glucuronidation of its substrates, including atorvastatin and telmisartan.
Reviewer notes (verbatim)
與fibrates較無關
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -82 bp
- Predicted consequence
- Blunted receptor-mediated induction of UGT1A3, dampening the inducible glucuronidation of lipophilic clinical substrates such as atorvastatin and fibrates.
- Prior narrative
- Blunted receptor-mediated induction of UGT1A3, dampening the inducible glucuronidation of lipophilic clinical substrates such as atorvastatin and fibrates.
- Drug context
- deferasirox; telmisartan; atorvastatin; montelukast; atazanavir; ritonavir
Submitted decision (verbatim): 接受
Reviewer notes (verbatim)
Blunted PXR-mediated induction of UGT1A4 may attenuate induction-related increases in substrate glucuronidation and clearance, resulting in higher exposure to substrates such as lamotrigine.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- at promoter -22 bp
- Predicted consequence
- Blunted receptor-mediated induction of UGT1A4, leading to attenuated clearance and increased systemic exposure of its clinical substrates such as lamotrigine.
- Prior narrative
- Blunted receptor-mediated induction of UGT1A4, leading to attenuated clearance and increased systemic exposure of its clinical substrates such as lamotrigine.
- Drug context
- lamotrigine; tamoxifen; ABT-751; anastrozole; testosterone
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated induction of UGT1A6 may attenuate inducible glucuronidation of its substrates.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- overlapping TSS
- Predicted consequence
- Blunted receptor-mediated induction of UGT1A6, restricting the inducible glucuronidation capacity of critical small-molecule drugs.
- Prior narrative
- Blunted receptor-mediated induction of UGT1A6, restricting the inducible glucuronidation capacity of critical small-molecule drugs.
- Drug context
- valproic acid; aspirin; irinotecan; oxaliplatin; tegafur / gimeracil / oteracil; deferiprone
Submitted decision (verbatim): 接受
Reviewer notes (verbatim)
Critical clinical substrates 可以改為較中性的措辭。Blunted receptor-mediated induction of UGT1A9, attenuating the inducible glucuronidation capacity of substrates such as mycophenolic acid and propofol.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- in distal enhancer +19740 bp
- Predicted consequence
- Blunted receptor-mediated induction of UGT1A9, attenuating the inducible glucuronidation capacity of critical clinical substrates such as mycophenolic acid and propofol.
- Prior narrative
- Blunted receptor-mediated induction of UGT1A9, attenuating the inducible glucuronidation capacity of critical clinical substrates such as mycophenolic acid and propofol.
- Drug context
- SN-38; irinotecan; propofol; sorafenib; mycophenolate mofetil; cotinine glucuronide
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Blunted PXR-mediated modulation of UGT2B7 may alter the glucuronidation of its substrates, including certain antiepileptic drugs and opioid analgesics, affecting parent-drug exposure and glucuronide metabolite formation.
Reviewer notes (verbatim)
對immunosuppressant substrates較無影響
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Rifampicin
- Regulatory element
- in distal enhancer +14718 bp
- Predicted consequence
- Blunted receptor-mediated modulation of UGT2B7, altering the adaptive clearance rate of heavily utilized opioid and immunosuppressant substrates.
- Prior narrative
- Blunted receptor-mediated modulation of UGT2B7, altering the adaptive clearance rate of heavily utilized opioid and immunosuppressant substrates.
- Drug context
- lamotrigine; valproic acid; morphine; oxcarbazepine; fentanyl; zidovudine
AhR axis
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Reduced AhR-mediated induction of ALDH3A1 would lower ALDH3A1-mediated oxidation of aldophosphamide; increased retention of the active intermediate may sensitise tumour cells to cyclophosphamide.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Smoking; PAHs; Experimental TCDD
- Regulatory element
- overlapping the TSS
- Predicted consequence
- Reduced AhR-mediated induction of ALDH3A1 would lower ALDH3A1-mediated oxidation of aldophosphamide; increased retention of the active intermediate may sensitise tumour cells to cyclophosphamide.
- Prior narrative
- Reduced AhR-mediated induction of ALDH3A1 would lower ALDH3A1-mediated oxidation of aldophosphamide; increased retention of the active intermediate may sensitise tumour cells to cyclophosphamide.
- Drug context
- cyclophosphamide; doxorubicin; fluorouracil
Submitted decision (verbatim): 接受
Reviewer notes (verbatim)
Diminished AhR-mediated transactivation of CYP1A1, reducing both basal and inducible CYP1A1 expression and thereby attenuating local bioactivation of procarcinogens such as benzo[a]pyrene.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Smoking; PAHs; Experimental TCDD
- Regulatory element
- at promoter -276 bp
- Predicted consequence
- Diminished AhR-mediated transactivation of CYP1A1, reducing both basal and inducible CYP1A1 expression and thereby attenuating local bioactivation of procarcinogens such as benzo[a]pyrene.
- Prior narrative
- Diminished AhR-mediated transactivation of CYP1A1, reducing both basal and inducible CYP1A1 expression and thereby attenuating local bioactivation of procarcinogens such as benzo[a]pyrene.
- Drug context
- deferasirox; carbamazepine; phenobarbital; phenytoin; valproic acid; capecitabine
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Reduced receptor-mediated transactivation of CYP1A2 diminishes the inducibility of this major hepatic CYP; substrate clearance is correspondingly less enhanced in the induced state, which may raise exposure to narrow-therapeutic substrates.
Reviewer notes (verbatim)
1. 臨床效應主要表現於移除誘導物（多為吸菸）暴露後之上調幅度減弱（住院後戒菸），較少見 severe interactions 2. 受影響受質藥物（PharmGKB 臨床註釋）：clozapine; caffeine; clopidogrel; paroxetine; olanzapine; deferasirox。可考慮將 clopidogrel, deferasirox 更換為同在PharmGKB 臨床註釋的 leflunomide, escitalopram。
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Smoking; PAHs; Experimental TCDD
- Regulatory element
- at promoter -3123 bp
- Predicted consequence
- Reduced receptor-mediated transactivation of CYP1A2 diminishes the inducibility of this major hepatic CYP; substrate clearance is correspondingly less enhanced in the induced state, which may raise exposure to narrow-therapeutic substrates.
- Prior narrative
- Reduced receptor-mediated transactivation of CYP1A2 diminishes the inducibility of this major hepatic CYP; substrate clearance is correspondingly less enhanced in the induced state, which may raise exposure to narrow-therapeutic substrates.
- Drug context
- clozapine; caffeine; leflunomide; paroxetine; olanzapine; escitalopram
Submitted decision (verbatim): 需修訂
Reviewer revision (verbatim)
Impaired receptor-mediated signaling that attenuates both the basal constitutive expression and chemical inducibility of CYP1B1 in chromatin context, lowering the localized pathway of estradiol 4-hydroxylation and procarcinogen activation that underlies tissue-specific susceptibility to malignancies.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Inducer
- Smoking; PAHs; Experimental TCDD
- Regulatory element
- overlapping TSS
- Predicted consequence
- Impaired receptor-mediated signaling that abolishes both the basal constitutive expression and chemical inducibility of CYP1B1 in extrahepatic tissues, perturbing the localized pathway of estradiol 4-hydroxylation and procarcinogen activation that drives tissue-specific susceptibility to malignancies.
- Prior narrative
- Impaired receptor-mediated signaling that abolishes both the basal constitutive expression and chemical inducibility of CYP1B1 in extrahepatic tissues, perturbing the localized pathway of estradiol 4-hydroxylation and procarcinogen activation that drives tissue-specific susceptibility to malignancies.
- Drug context
- cyclophosphamide; doxorubicin; fluorouracil; risperidone; epirubicin; paclitaxel
Tier 2: reviewed literature reference panel (7 records)
These literature reference records are separate from the peak-anchored panel above. Their inclusion does not establish a receptor-bound element in this ChIP-seq panel. Submitted decisions and notes are retained, including reviews that request revision without providing replacement text.
Submitted decision (verbatim): 需修訂
Reviewer notes (verbatim)
CYP2B6 的誘導在 PBREM 不完全由 CAR (NR1I3) 主導（PMID: 23840296）
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- efavirenz; bupropion; methadone; cyclophosphamide; ketamine
- Nearest peak (bp)
- 69882
- Panel context
- CYP2B6 induction is CAR (NR1I3)-DOMINATED at the PBREM, not PXR-driven. AetherXeno profiles only PXR/FXR/AhR (not CAR), so the absence of a proximal PXR peak is exactly what CAR-dominated regulation predicts — a specificity result, not a miss. CAR profiling is planned future work.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 需修訂
Reviewer notes (verbatim)
CYP2E1 的誘導主要是轉譯後（PMID: 8530344）
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- ethanol; volatile anaesthetics; acetaminophen (bioactivation)
- Nearest peak (bp)
- 197420
- Panel context
- CYP2E1 induction is largely POST-TRANSCRIPTIONAL (substrate-mediated protein stabilization), not receptor-transcriptional — so the absence of a PXR peak is mechanistically expected, not a miss.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- bile-acid / cholesterol homeostasis (rate-limiting enzyme)
- Nearest peak (bp)
- 2257281
- Panel context
- FXR represses CYP7A1 INDIRECTLY via SHP/NR0B2, with no direct FXR binding at the CYP7A1 promoter — textbook. The absence of an FXR peak is EXPECTED and biologically correct; the direct mediator NR0B2/SHP IS peak-supported in Tier 1.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 需修訂
Reviewer notes (verbatim)
FMO3 expression is induced by dietary bile acids by a mechanism that involves the farnesoid X receptor (FXR), a bile acid-activated nuclear receptor（PMID: 23312283）.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- benzydamine; trimethylamine; some tertiary amines
- Nearest peak (bp)
- 115526
- Panel context
- FMO3 is mainly developmentally/constitutively regulated rather than xenobiotic-induced; nearest peak distal (116 kb) — no proximal PXR peak.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 需修訂
Reviewer notes (verbatim)
A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity (PMID: 25275310).
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- busulfan; chlorambucil; electrophile detoxification
- Nearest peak (bp)
- 57917
- Panel context
- GSTA1 is predominantly Nrf2(ARE)- and AhR-controlled; the PXR contribution is minor, so the absence of a proximal PXR peak is consistent with Nrf2/AhR-dominant regulation.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 需修訂
Reviewer notes (verbatim)
Digoxin 非 OATP1B3 受質
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- statins; telmisartan; digoxin; fexofenadine
- Nearest peak (bp)
- 434299
- Panel context
- OATP1B3 is regulated more by FXR/HNF than PXR; there is no proximal PXR element (nearest peak 434 kb). No binding claim.
- Claim type
- clinical_reference_no_binding_claim
Submitted decision (verbatim): 接受
No revision text or notes were submitted.
Prior explanatory context
Retained explanatory context, not the pharmacist's submitted wording. The submitted review above takes precedence; this context is not a replacement for the reviewer's revision or notes.
- Drug context
- oral-drug intestinal glucuronidation
- Nearest peak (bp)
- 73993
- Panel context
- UGT1A8 is likewise INTESTINE-predominant; not captured by a liver ChIP atlas (tissue specificity; nearest peak 74 kb).
- Claim type
- clinical_reference_no_binding_claim
Drug context may represent a substrate, inhibitor, inducer, prodrug or other literature-supported association; it should not be interpreted as a uniform substrate classification. Causal chains describe mechanism only and are scientific predictions, not medical advice.