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Table 8 Examples of inferred drug drug interactions and supportive evidence from literature

From: Extracting drug-enzyme relation from literature as evidence for drug drug interaction

Drugs with interaction

Enzyme

Evidence

Carbamazepine/oxcarbazepine quinidine

CYP3A4

We performed a study in healthy volunteers to investigate the relative inductive effect of CBZ and OXCZ on CYP3A4 activity using the metabolism of quinidine as a biomarker reaction…We confirm a clinically significant inductive effect of both OXCZ and CBZ. (PMID: 17346248)

Lidocaine fluvoxamine

CYP1A2

Lidocaine is metabolized by cytochrome P450 3A4 (CYP3A4) and CYP1A2 enzymes…We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces the presystemic metabolism of oral lidocaine… (PMID: 16918719)

Quinidine itraconazole

CYP3A4

Quinidine is eliminated mainly by CYP3A4-mediated metabolism… Itraconazole increases plasma concentrations of oral quinidine, probably by inhibiting the CYP3A4 isozyme during the first-pass and elimination phases of quinidine. (PMID: 9390107)

Propofol orphenadrine

CYP2B6

Involvement of human liver cytochrome P4502B6 in the metabolism of propofol… orphenadrine, a CYP2B6 inhibitor, reduced the rate constant of propofol by liver microsomes by 38 % (P < 0.05)… (PMID: 11298076)

Rifalazil fluconazole

CYP3A4

Rifalazil-32-hydroxylation in microsomes was completely inhibited by CYP3A4-specific inhibitors (fluconazole, …) … indicating that the enzyme responsible for the rifalazil-32-hydroxylation is CYP3A4. (PMID: 10923859)