Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · May 2012
Clinical pharmacology and orphan drugs: an informational inventory 2006-2010.
Clinical pharmacology can have an important impact on the development of orphan drugs, i.e., therapeutic agents for rare diseases. This topic was explored at a US Food and Drug Administration (FDA) Advisory Committee meeting in March 2011.1 At that meeting, preliminary data were presented regarding the breakdown of the clinical pharmacology content in the approvals for orphan drugs in 2006–2010. These data, along with follow-up observations, are presented here, focusing on the in vivo study content and the relevant populations.
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Clin. Pharmacol. Ther. · Apr 2012
Comparative StudyMechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.
Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. ⋯ Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics.
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Clin. Pharmacol. Ther. · Apr 2012
Comparative StudyThe role and impact of research agendas on the comparative-effectiveness research among antihyperlipidemics.
Although it is well established that funding source influences the publication of clinical trials, relatively little is known about how funding influences trial design. We examined a public trial registry to determine how funding source shapes trial design among trials involving antihyperlipidemics. We used an automated process to identify and analyze 809 trials from a set of 72,564. ⋯ The results indicated that industry-funded trials were more likely to compare across drugs and examine dyslipidemia as a condition, and less likely to register safety outcomes. The source of funding for clinical trials had a measurable effect on trial design, which helps quantify differences in research agendas. Improved monitoring of current clinical trials may be used to more closely align research agendas to clinical needs.