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.
Amsden
Guy W
GW
Clinical Pharmacology Research Center, Department of Adult and Pediatric Medicine, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326, USA.
Whitaker
Anne-Marie
AM
Johnson
Patrick W
PW
D000328:Adult; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001628:Beverages; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002957:Citrus; D018592:Cross-Over Studies; D002523:Edible Grain; D005215:Fasting; D005260:Female; D005527:Food, Fortified; D018565:Food-Drug Interactions; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D008892:Milk; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D000890:Anti-Infective Agents; D002136:Calcium, Dietary; D064704:Levofloxacin; D015242:Ofloxacin