British journal of clinical pharmacology
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Br J Clin Pharmacol · Apr 2008
Randomized Controlled TrialEffect of single doses of maraviroc on the QT/QTc interval in healthy subjects.
To assess the effect of a single dose of maraviroc on the QTc interval in healthy subjects and to evaluate the QTc interval-concentration relationship. ⋯ Single doses of maraviroc, up to and including 900 mg, had no clinically relevant effect on QTcF or QTcI. At all maraviroc doses and for both end-points, the mean difference from placebo for QTc was < 4 ms. There was no apparent relationship between QT interval and maraviroc plasma concentration up to 2363 ng ml(-1). This conclusion held in both male and female subjects, and there was no evidence of a change in the QT/RR relationship with concentration.
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Br J Clin Pharmacol · Apr 2008
Randomized Controlled TrialEffects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers.
To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist. ⋯ Potent CYP3A4 inhibitors, including ketoconazole and protease inhibitors (except TPV/r), increase maraviroc exposure. Downward adjustment of the maraviroc dose during co-administration with protease inhibitors can compensate for the interaction. TPV/r does not affect the steady-state pharmacokinetics of maraviroc, and hence no dose adjustment would be warranted.
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Br J Clin Pharmacol · Jan 2008
Randomized Controlled Trial Multicenter Study Comparative StudyA comparison of serum antivenom concentrations after intravenous and intramuscular administration of redback (widow) spider antivenom.
There are no studies measuring antivenom concentrations following intramuscular administration. This study aimed to compare antivenom concentrations following intravenous and intramuscular administration of redback spider antivenom (RBSAV). ⋯ RBS AV given by the intramuscular route is unlikely to be effective in the treatment of redback (widow) spider bite.
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Br J Clin Pharmacol · Dec 2007
Randomized Controlled Trial Comparative StudyEffect of dronedarone on renal function in healthy subjects.
To assess the effects of dronedarone on renal function and tubular cation handling. ⋯ Dronedarone reduces renal creatinine and NMN clearance by about 18%, without evidence of an effect on GFR, renal plasma flow or electrolyte exchanges. This suggests a specific partial inhibition of tubular organic cation transporters (OCT). A limited increase in serum creatinine is therefore expected with dronedarone treatment, but does not mean there is a decline in renal function.
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Br J Clin Pharmacol · Sep 2007
Randomized Controlled TrialThe pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects.
The novel direct thrombin inhibitor (DTI), dabigatran etexilate (Boehringer Ingelheim Pharma GmbH & Co. KG), shows potential as an oral antithrombotic agent. Two double-blind, randomized trials were undertaken to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of orally administered dabigatran etexilate in healthy male subjects. ⋯ These data suggest that dabigatran etexilate is a promising novel oral DTI with predictable PK and PD characteristics and good tolerability. Further investigation of dabigatran etexilate for the treatment and prophylaxis of patients with arterial and venous thromboembolic disorders, acute coronary syndromes and other medical conditions is warranted.