British journal of clinical pharmacology
-
Br J Clin Pharmacol · Jul 2010
Randomized Controlled Trial Comparative StudyPharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers.
The antiplatelet agent clopidogrel is currently the recommended treatment for acute coronary syndrome (ACS). Inhibition of platelet aggregation (IPA) with clopidogrel is insufficient, which increases the risk for recurrent ischaemic events. Therefore, there is a need for antiplatelet agents with improved IPA. Ticagrelor (AZD6140) is a new antiplatelet agent in clinical development for reduction of thrombotic events in patients with ACS. ⋯ Multiple dosing provided predictable pharmacokinetics of ticagrelor and its metabolite over the dose range of 50-600 mg once daily and 50-300 mg twice daily with C(max) and AUC(0,t) increasing approximately dose-proportionally. Greater and more consistent IPA with ticagrelor at doses > or = 100 mg twice daily and > or = 300 mg once daily were observed than with clopidogrel. Ticagrelor at doses up to 600 mg day(-1) was well tolerated.
-
Br J Clin Pharmacol · Apr 2010
Randomized Controlled TrialNo cardiac effects of therapeutic and supratherapeutic doses of rupatadine: results from a 'thorough QT/QTc study' performed according to ICH guidelines.
To evaluate the effects of therapeutic and supratherapeutic doses of rupatadine on cardiac repolarization in line with a 'thorough QT/QTc study' protocol performed according to International Conference on Harmonization guidelines. ⋯ This 'thorough QT/QTc study' confirmed previous experience with rupatadine and demonstrated that it had no proarrhythmic potential and raised no concerns regarding its cardiac safety.
-
Br J Clin Pharmacol · Dec 2009
Randomized Controlled TrialPharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype.
* Pharmacokinetic variability of voriconazole is largely caused by CYP3A4- and CYP2C19-mediated metabolism. * Oral bioavailability of voriconazole has been claimed to be almost 100%, thus facilitating a change from intravenous to oral application without dose adjustment. ⋯ Independent of the route of administration, voriconazole exposure was three times higher in CYP2C19 poor metabolizers compared with extensive metabolizers. Voriconazole has a high bioavailability with no large differences between the CYP2C19 genotypes. The hydroxylation pathway of voriconazole elimination exceeded the N-oxidation, both influenced by the CYP2C19 genotype.
-
Br J Clin Pharmacol · Oct 2009
Randomized Controlled Trial Comparative StudyA comparison of two formulations of intradermal capsaicin as models of neuropathic pain in healthy volunteers.
To compare the dose-response relationships of two formulations [Tween- or hydroxypropyl-b-cyclodextrin (HP-b-CD)-based] of intradermal capsaicin in healthy volunteers and to assess the effect of potential covariates of response. One, 10, 30 and 100 microg in 10 ml were compared for the outcomes of flare, spontaneous pain, mechanical allodynia and hyperalgesia in eight healthy men and eight healthy women. ⋯ The formulations are comparable over the dose range 1-30 microg. The significantly lower pain response at the 100 microg dose in the Tween compared with the HP-beta-CD formulation is likely to be due to limitations in solubility at the 100 microg level. Given the greater ease of formulation and the superior dose-response relationship, the HP-beta-CD formulation is preferable for use in the model in future studies.
-
Br J Clin Pharmacol · Mar 2009
Randomized Controlled Trial Meta Analysis Comparative StudyPain on injection with microemulsion propofol.
To evaluate the incidence and severity of injection pain caused by microemulsion propofol and lipid emulsion propofol in relation to plasma bradykinin generation and aqueous free propofol concentrations. ⋯ Higher aqueous free propofol concentrations of microemulsion propofol produce more frequent and severe pain. The plasma kallikrein-kinin system may not be involved, and the agents that reduce injection pain may not act by decreasing aqueous free propofol concentrations.