British journal of clinical pharmacology
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Br J Clin Pharmacol · Jun 2015
Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005-2011.
The aim of the study was to analyze the prescribing pattern of both newer and older AEDs. ⋯ Older AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin.
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Br J Clin Pharmacol · Jun 2015
The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort.
Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care. ⋯ Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.
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Br J Clin Pharmacol · Jun 2015
Evaluation of drug-drug interactions for oncology therapies: in vitro-in vivo extrapolation model-based risk assessment.
Understanding drug-drug interactions (DDI) is a critical part of the drug development process as polypharmacy has become commonplace in many therapeutic areas including the cancer patient population. The objectives of this study were to investigate cytochrome P450 (CYP)-mediated DDI profiles available for therapies used in the oncology setting and evaluate how models based on in vitro-in vivo extrapolation performed in predicting CYP-mediated DDI risk. ⋯ This work illustrates the utility and limitations of current DDI risk assessment approaches applied to a range of contemporary anti-cancer agents, and discusses the implications for therapeutic combination strategies.
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Br J Clin Pharmacol · May 2015
Randomized Controlled TrialCharacterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist.
Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy. ⋯ The integrated CIDV PK/PD model provides a useful platform for characterization of PK/PD relationships and predictions of dose-response relationships to aid in future development of CGRP and TRPV1 receptor antagonists.