The effect of omeprazole on the bioavailability and safety of garenoxacin in healthy volunteers
Abstract number: 1134_02_295
Kisicki J., Krishna G., Olsen S., Grasela D.
The novel des-F(6)-quinolone garenoxacin (GRN) is more soluble in acidic conditions than at neutral pH. Therefore, this study was designed to determine if omeprazole affects the bioavailability of GRN.
This non-randomized, open-label pharmacokinetic study was conducted in healthy adult subjects. On day 1, the single-dose pharmacokinetics of 600 mg of oral GRN (one 200 and one 400 mg tablet) were determined in fasting subjects, with serial blood samples obtained through 72 hours post-dose. Omeprazole 40 mg was administered once daily on days 4 to 7 to achieve steady-state inhibition of gastric acid secretion. On day 8, single doses of GRN and omeprazole were administered concomitantly. Omeprazole treatment was continued on days 9 and 10 throughout the period of pharmacokinetic blood sampling. Study assessments included vital signs and physical, laboratory, and electrocardiographic examinations for safety.
Fourteen subjects (8 male; mean age, 25 years) were enrolled and 12 completed the study. Concomitant administration of omeprazole did not affect the AUC (INF) or Cmax of GRN. The geometric mean (GM) for GRN AUC(INF) was 132.0 mcg.h/mL, compared with 140.4 mcg.h/mL for concomitant GRN and omeprazole [90% confidence interval (CI) 101111%]. The GM Cmax value for GRN and GRN/omeprazole co-administration was 9.6 and 9.3 mcg/mL, respectively, with 90% CI of 90% to 104%. Half-life (mean range 12.9 to 14 h) and Tmax (median range 1.5 to 1.8 h) were similar after administration of GRN either alone or concomitantly with omeprazole. Concomitant administration of garenoxacin and omeprazole was well tolerated. Nine of 14 subjects (64%) experienced a total of 33 adverse events (AEs). The majority of AEs were mild, and only 12 were deemed possibly or probably related to the study drug. The most frequently cited AEs, headache, nausea and abdominal pain, were mild to moderate in severity. Two subjects withdrew from the study; neither discontinuation was due to AEs.
The concomitant administration of omeprazole had no effect on garenoxacin bioavailability. These findings indicate that garenoxacin can be administered with omeprazole or other agents that affect gastric pH to a similar or lesser extent.
|Session name:||XXIst ISTH Congress|
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