Characterization of the penetration of garenoxacin into the breast milk of lactating women.

The primary objective of this study was to characterize the extent of excretion of garenoxacin, a novel des-F(6)-quinolone antimicrobial, into the breast milk of lactating women. A secondary objective was to determine the time after dose administration that garenoxacin was no longer detected in breast milk so as to define when a mother may resume breastfeeding if it was interrupted for garenoxacin administration. Six healthy, lactating women (age [mean +/- SD]: 32 +/- 6 years; weight: 68.3 +/- 19.8 kg; body mass index: 26 +/- 5 kg/m(2)) who had completed weaning their infants were administered a single 600-mg oral dose of garenoxacin. Plasma samples were collected predose and repeatedly up to 72 hours postdose. Breast milk was collected predose and for 6- to 12-hour intervals repeatedly up to 120 hours postdose. Breast milk/plasma concentration ratios for garenoxacin ranged from 0.35 to 0.44 up to 24 hours postdose, and the mean peak breast milk concentration was 3.0 microg/mL (0- to 6-h collection interval). Overall, garenoxacin exposure in breast milk was minimal, with a mean of 0.07% of the administered dose recovered within 120 hours. Indeed, garenoxacin was undetectable in the breast milk of a majority of subjects within 84 hours of dosing. As such, an infant nursing from a mother who had received a single 600-mg oral dose of garenoxacin could theoretically be exposed to 0.42 mg of garenoxacin (0.105 mg/kg/day for a 4-kg infant over the period of 5 days of nursing). If extrapolated to a 14-day course of garenoxacin 600 mg once daily, total exposure would be approximately 5.88 mg. These findings indicate that, like other quinolone antimicrobials, garenoxacin is secreted in breast milk.

Lack of bioequivalence of levofloxacin when coadministered with a mineral-fortified breakfast of juice and cereal.

Previous studies have demonstrated that the chelation interactions demonstrated between fluoroquinolones and antacids also occur when they are coadministered with mineral-fortified foods. This study was conducted to evaluate the bioequivalence of levofloxacin when administered in a fasting state as compared to when it was administered with a common breakfast of calcium-fortified orange juice and ready-to-eat cereal. Fourteen of 16 healthy volunteers completed this study and received 500 mg of levofloxacin with each of the following: (1) 12 ounces of water, (2) subject-measured portions of juice and cereal, and (3) subject-measured portions of juice and cereal with milk. Plasma samples were collected prior to dosing and for up to 48 hours after. The results demonstrated that neither fed phase was bioequivalent to the fasting arm in terms of Cmax (with milk, 79.2% [72.6%, 85.7%]; without milk, 79.1% [73.3%, 84.9%]). In addition, a weak correlation was identified between the amount of change in 24-hour exposure and mineral fortification. The results of this study further demonstrate a need to require additional fed-fasted bioequivalence studies for drugs that demonstrate no interaction with the FDA meal but have significant interactions with drugs or supplements that contain large amounts of multivalent ions.