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OBJECTIVES Valspodar is a P-glycoprotein modulator currently under development as a multidrug resistance reversal agent in clinical oncology. A multiple-dose drug interaction study was performed to assess the influence of valspodar on digoxin, a substrate for P-glycoprotein. METHODS Twelve healthy volunteers received an oral digoxin loading dose of 1 mg(More)
Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P450IA2 (CYP1A2) activity in vivo, the 13C-[N-3-methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S-mephenytoin. Breath tests were performed before(More)
Caffeine is used to phenotype subjects in vivo for the cytochrome P450 isoforms CYP1A2 and CYP2E1, and for N-acetyltransferase type 2 (NAT2). However, how much of the variation in phenotyping parameters may be attributed to variations in CYP1A2 and CYP2E1 activities has not been determined. Therefore, this study intraindividually compared enzyme activities(More)
INTRODUCTION This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote hydroxocobalamin. METHODS Four ascending dosing groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over 7.5 to 30 minutes at a constant infusion rate.(More)
Several procedures to monitor CYP1A2 activity in vivo by the use of caffeine as a probe have been proposed. They comprise caffeine clearance, based on both plasma and saliva concentrations, urinary metabolite ratios, the 13C-caffeine breath test, and the paraxanthine/caffeine ratio in plasma. The latter method is fast, simple, economical and restricted to(More)
To assess whether or not concomitant omeprazole treatment influences the pharmacokinetics of lomefloxacin and ciprofloxacin, a randomized, double-blind four-way-crossover study was performed. Another objective was to compare the pharmacokinetics of lomefloxacin and ciprofloxacin. Twelve healthy volunteers participated. On days 1 to 4 of each study period,(More)
S-Mephenytoin 4'-hydroxylase (CYP2C19) is a genetically polymorphic cytochrome P450. A modified method for CYP2C19 phenotyping was evaluated in 174 healthy German volunteers and the results were compared with genotyping for the intron4/exon5 G-->A splice site mutation (m1) of CYP2C19, associated with the poor metabolizer (PM) phenotype. A smaller than usual(More)
BACKGROUND Omeprazole has previously been shown to induce hepatic cytochrome P4501A2 activity, as evidenced by an accelerated N-3-demethylation in the 13C-[N-3-methyl]-caffeine breath test. In this study we investigated whether the inducing potency of omeprazole can be quantified by the determination of urinary caffeine metabolite ratios, which are based on(More)
Gemifloxacin is a novel fluoroquinolone, currently in development for the treatment of respiratory tract infections. This double-blind (with respect to gemifloxacin), randomized, crossover study investigated the possibility of pharmacokinetic interaction between gemifloxacin and theophylline. After a 4-8-day run-in phase to establish the dose of(More)
Gemifloxacin is a novel fluoroquinolone with a broad spectrum of activity. This double-blind, randomized, parallel-group study was designed to demonstrate the lack of effect of steady-state concentrations of gemifloxacin on the pharmacodynamic effects of warfarin. Healthy male subjects received loading doses of warfarin on days 1 and 2. The warfarin dose(More)