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The effect of Maalox on bioavailability and safety of garenoxacin in healthy volunteers

Abstract number: 1134_02_296

Kisicki J., Krishna G., Olsen S., Grasela D.

Objective:

Garenoxacin (GRN) is a novel broad-spectrum des-F(6)-quinolone antibiotic. Quinolones are known to chelate with cations such as aluminum, impairing antibiotic absorption. This study was therefore designed to assess the effect of a 20-mL dose of Maalox® (containing 900 mg aluminum hydroxide and 800 mg magnesium hydroxide) on the pharmacokinetics of GRN when administered concomitantly with, 2 and 4 hours before, and 2 and 4 hours after, Maalox.

Methods:

This was a randomized, open-label, 6-treatment, control-balanced, residual effects design pharmacokinetic study. The 6 oral treatments consisted of 600 mg GRN (one 200 and one 400 mg GRN tablet) given alone, with concomitant Maalox, 2 h before Maalox, 4 h before Maalox, 2 h after Maalox, and 4 h after Maalox. Each healthy adult subject received 3 of the above treatments, with a 7-day washout period between treatments. In each treatment, serial blood samples for pharmacokinetic analysis were collected before and up to 72 h after GRN dosing. Study assessments included vital signs and physical, laboratory, and electrocardiographic examinations for drug safety.

Results:

Twenty subjects (12 male, 8 females; mean age, 27 years) were enrolled. Exposure to GRN [AUC(INF)] was reduced by 58% when coadministered with Maalox. Exposure to GRN was also reduced when administered 2 or 4 hours after Maalox, by 22% and 16%, respectively. In contrast, when administered 4 hours before Maalox, GRN exposure was not affected. When GRN was administered 2 hours before Maalox, a small reduction (12%) in GRN exposure was observed that is unlikely to be clinically relevant. Half-life (mean range 11.5 to 14.2 hours) and Tmax (median range 1.5 to 2 hours) were similar across treatment groups. A single oral 600 mg dose of GRN was well tolerated. Mild adverse events were reported by 2 subjects; 1 subject discontinued due to mild abdominal pain and blood in the stool.

Conclusions:

Maalox does not affect GRN bioavailability when GRN is administered at least 2 h prior to Maalox. However, a reduction in GRN exposure is observed when GRN is administered concomitantly or up to 4 h after Maalox. Therefore, GRN can be administered 2 h before or 4 h after administration of Maalox or other products containing a high content of cations, particularly aluminum.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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