No pharmacokinetic drug-drug interaction between nevirapine and paclitaxel.
We have investigated the pharmacokinetics of nevirapine and paclitaxel in a patient who used both drugs concomitantly, as there are strong theoretical indications for a potential pharmacokinetic drug-drug interaction. Plasma concentrations of nevirapine (dose: 200 mg twice daily orally) and paclitaxel (dose: 100 mg/m(2) 3-h i.v. infusion) were determined in a HIV-1-infected patient with Kaposi's sarcoma. Since both drugs are metabolized via the same cytochrome P450 isoenzymes, investigation of a drug-drug interaction was considered important. We found that the plasma concentrations of nevirapine given together with paclitaxel were similar to those given without paclitaxel. The exposures to paclitaxel (AUC(0-infinity) = 3787 h.ng/ml) and its hydroxy metabolites when co-administered with nevirapine were comparable to the mean exposure to paclitaxel and its metabolites from eight historical controls (AUC(0-infinity) = 3614 h.ng/ml) treated with the same dose. No pharmacokinetic drug-drug interaction between nevirapine and paclitaxel could be demonstrated in our HIV-1-infected patient.
Kappelhoff
Bregt S
BS
Departments of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands. apbkp@slz.nl
Huitema
Alwin D R
AD
Mairuhu
Albert T A
AT
Schellens
Jan H M
JH
Beijnen
Jos H
JH
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D004347:Drug Interactions; D016903:Drug Monitoring; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007866:Leg; D008297:Male; D019829:Nevirapine / Q000493:pharmacokinetics*; D017239:Paclitaxel / Q000493:pharmacokinetics*; D010157:Palatal Neoplasms / Q000188:drug therapy / Q000209:etiology; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000209:etiology; D018119:Stavudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000972:Antineoplastic Agents, Phytogenic; D019259:Lamivudine; D003577:Cytochrome P-450 Enzyme System; D019829:Nevirapine; D018119:Stavudine; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017239:Paclitaxel