Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 2007
Multicenter StudyG protein beta3 polymorphism and triptan response in cluster headache.
Only about 70% of migraine and cluster headache (CH) patients report significant treatment responses to triptans, which are agonists at 5-HT(1B/D) receptors belonging to the family of G protein-coupled receptors. We analyzed whether a common polymorphism in the gene for the G protein beta3 subunit (GNB3 C825T) modulates responder rates to triptans among a cohort of 231 unrelated Caucasian CH patients. ⋯ The GNB3 genotype status did not affect responses to other acute and preventive therapeutic regimes including oxygen, verapamil, and corticosteroids, i.e., drugs not directly affecting G proteins. We conclude that pain relief by triptans is significantly modulated by a common genetic GNB3 variant.
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Clin. Pharmacol. Ther. · Aug 2007
ReviewRegulatory considerations for determining postmarketing study commitments.
Postmarketing Study Commitments (PMCs) are, most commonly, agreements made by pharmaceutical companies at the time of an FDA approval to perform a study or studies to elucidate further characteristics of the drug under consideration. The role of PMCs in drug regulation has come under considerable scrutiny in recent years, particularly as discussions of drug safety have intensified. ⋯ When made, PMCs are described in the approval letters and are therefore publicly available. Concerns over whether PMCs were being duly performed, reported, and reviewed by FDA were addressed in the FDA Modernization Act of 1997, which required more detailed reporting by manufactures on their progress in meeting the PMCs and required FDA to report certain information publicly.
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Clin. Pharmacol. Ther. · Aug 2007
The pharmaceutical industry at risk: how excessive government regulation stifles innovation.
In the fall of 2006, I published a book, Overdose: How Excessive Government Regulation Stifles Pharmaceutical Innovation. The book goes against the conventional wisdom found in the academic and popular literature on the topic by offering a more sympathetic view of the pharmaceutical industry.
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Clin. Pharmacol. Ther. · Jul 2007
Comparative Study Clinical TrialConcentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes.
The influence of CYP2D6 genotype and CYP2D6 inhibitors on enantiomeric plasma levels of tramadol and O-desmethyltramadol as well as response to tramadol was investigated. One hundred and seventy-four patients received one hundred intravenous tramadol 3 mg/kg for postoperative analgesia. Blood samples drawn 30, 90, and 180 min after administration were analyzed for plasma concentrations of the enantiomers (+)-, (-)tramadol and (+)-, (-)O-desmethyltramadol by liquid chromatography-tandem mass spectrometry. ⋯ Comedication with CYP2D6 inhibitors decreased (+) O-desmethyltramadol concentrations (P<0.01). In PMs, non-response rates to tramadol treatment increased fourfold compared with the other genotypes (P<0.001). In conclusion, CYP2D6 genotype determined concentrations of O-desmethyltramadol enantiomers and influenced efficacy of tramadol treatment.