Lack of Bioequivalence of Levofloxacin When Coadministered with a Mineral‐Fortified Breakfast of Juice and Cereal

Abstract

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.

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

“…Mean values for pharmacokinetic parameters C max (reference: 5.69 µg/mL; test: 5.67 µg/mL), T max (reference: 1.60 h; test: 1.29 h), AUC 0-t (reference: 41.52 µg·h/mL; test: 39.22 µg·h/mL), AUC 0-inf (reference: 45.50 µg·h/mL; test: 44.24 µg·h/mL) and T 1/2el (reference: 6.55 hours; test: 6.69 hours) were similar to that reported by other authors (Amsden, Whitaker, Johnson, 2003;Chien et al, 1997;Lee et al, 1997;Lubasch et al, 2000;Wagenlehner et al, 2006). ANOVA revealed the absence of sequence effect for C max , AUC 0-t e AUC 0-inf .…”

Febrile Infection in Post-Prostate Biopsy: Results of a Ten-Year Single-Institution Study in South Taiwan

“…We also found that the incidence of infectious complications was reduced further when patients were instructed thoroughly about the use of their prophylactic antimicrobial medications. Because mineral-fortified meals or drinks may interfere with the absorption of fluoroquinolones [30], it is important to let patients know the factors of which they should be aware in their use of these medications.…”

Interactions of medicines with dietic supplementsa

“…Orange juice supplemented with calcium may lead to the formation of chelate with fl uoroquinolones (ciprofl oxacin, gatifl oxacin, levofl oxacin) and tetracyclines (tetracycline, minocycline). Th e www.hophonline.org administration of levofl oxacin with food-rich calcium signifi cantly reduces its bioavailability [45]. Calcium also prevents the bisphosphonate absorption.…”