Selegiline transdermal system: an examination of the potential for CYP450-dependent pharmacokinetic interactions with 3 psychotropic medications.
ABSTRACT 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.
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ABSTRACT: Few methods are available to explore the impact of neurocognition in schizophrenia on behaviors performed in usual contexts. The authors developed a video ethnography approach to examine the relationship between naturalistic behaviors and research constructs of neurocognition. Video ethnographers accompanied subjects through usual routines gathering continuous video data. Researchers developed codes to measure four behavioral domains observed on video. This paper describes the psychometric characteristics to be considered in the development of observational approaches. It also highlights differences between behaviors performed in usual environments and neuropsychological constructs. The authors demonstrate that everyday behaviors that have been shown to correspond to neurocognitive skills in a pilot feasibility study can be identified and rated. They further suggest that observational methods could provide novel strategies for linking research findings and clinical concerns.The Journal of neuropsychiatry and clinical neurosciences 03/2012; 24(2):125-40. DOI:10.1176/appi.neuropsych.11080201 · 2.77 Impact Factor
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ABSTRACT: Food and Drug Administration (FDA) regulations mandate that package inserts (PIs) include observed or predicted clinically significant drug-drug interactions (DDIs), as well as the results of pharmacokinetic studies that establish the absence of effect. To quantify how frequently observed metabolic inhibition DDIs affecting US-marketed psychotropics are present in FDA-approved PIs and what influence the source of DDI information has on agreement between 3 DDI screening programs. The scientific literature and PIs were reviewed to determine all drug pairs for which there was rigorous evidence of a metabolic inhibition interaction or noninteraction. The DDIs were tabulated noting the source of evidence and the strength of agreement over chance. Descriptive statistics were used to examine the influence of source of DDI information on agreement among 3 DDI screening tools. Logistic regression was used to assess the influence of drug class, indication, generic status, regulatory approval date, and magnitude of effect on agreement between the literature and PI as well as agreement among the DDI screening tools. Thirty percent (13/44) of the metabolic inhibition DDIs affecting newer psychotropics were not mentioned in PIs. Drug class, indication, regulatory approval date, generic status, or magnitude of effect did not appear to be associated with more complete DDI information in PIs. DDIs found exclusively in PIs were 3.25 times more likely to be agreed upon by all 3 DDI screening tools than were those found exclusively in the literature. Generic status was inversely associated with agreement among the DDI screening tools (odds ratio 0.11; 95% CI 0.01 to 0.89). The presence in PIs of DDI information for newer psychotropics appears to have a strong influence on agreement among DDI screening tools. Users of DDI screening software should consult more than 1 source when considering interactions involving generic psychotropics.Annals of Pharmacotherapy 10/2012; 46(10):1287-98. DOI:10.1345/aph.1R150 · 2.92 Impact Factor
Future Neurology 11/2007; 2(6):601-611. DOI:10.2217/14796708.2.6.601