Selegiline transdermal system: an examination of the potential for CYP450-dependent pharmacokinetic interactions with 3 psychotropic medications.
Selegiline transdermal system (STS) is a recently approved monoamine oxidase inhibitor antidepressant. This article reports results from 3 studies examining the potential for cytochrome P450-dependent pharmacokinetic interactions between STS and 3 psychotropic medications that might be coadministered. Three open-label, randomized, Latin square, 3-sequence crossover design studies were conducted with healthy volunteers to determine the pharmacokinetic parameters of STS 6 mg/24 h and test drug (alprazolam, olanzapine, or risperidone) when administered alone and concomitantly. All pharmacokinetic parameters of interest were unaltered following selegiline or test drug monotherapy when compared to concomitant therapy. This was confirmed by least squares mean ratios and their 90% confidence intervals of log(e)-transformed C(max) and AUC(tau) values, using either standard bioequivalence criteria of 80% to 125% or study-defined 70% to 143% boundary criteria. These results demonstrate that STS 6 mg/24 h may provide an antidepressant option that is unlikely to result in CYP450-mediated pharmacokinetic drug-drug interactions.
Azzaro
Albert J
AJ
Chief Scientific Officer, Somerset Pharmaceuticals, Inc, Rocky Point Center, 3030 North Rocky Point Drive, Suite 250, Tampa, FL 33607, USA.
Ziemniak
John
J
Kemper
Eva
E
Campbell
Bryan J
BJ
VanDenBerg
Chad
C
D000279:Administration, Cutaneous; D000328:Adult; D000525:Alprazolam / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077152:Olanzapine; D018967:Risperidone / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D012642:Selegiline / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D008996:Monoamine Oxidase Inhibitors; D001569:Benzodiazepines; D012642:Selegiline; D003577:Cytochrome P-450 Enzyme System; D018967:Risperidone; D000077152:Olanzapine; D000525:Alprazolam