title: Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers.
abstract: Previous work has demonstrated that the chelation interaction seen with ciprofloxacin when it is coadministered with antacids also happens when it is coadministered with calcium-fortified foods. This study was conducted to study whether this was a drug-specific finding or whether the interaction occurs with other members of the fluoroquinolone class of drugs. Sixteen healthy volunteers received single 400-mg oral doses of gatifloxacin with 12 ounces each of water, nonfortified orange juice, and calcium-fortified orange juice and had plasma samples drawn for assay over the subsequent 48 hours. Results demonstrated significant increases in total oral clearance (15%) and volume of distribution (13%) along with a matching significant decrease (12%) in exposure (AUC) when gatifloxacin was taken with the fortified juice. Although not statistically significant, peak concentrations decreased by 15% and were reached (tmax) approximately 38% later when gatifloxacin was coadministered with the calcium-fortified juice. Bioavailability testing indicated that although the 90% confidence intervals (CIs) for the ratio of the geometric means of the calcium-fortified juice and water arms' AUC stayed within the range of 80% to 125%, those for Cmax did not. This study demonstrated a chelation or adsorption interaction between the fortified juice and gatifloxacin that reached regulatory significance. As a result, clinicians may wish to instruct patients to take gatifloxacin either with nonfortified foods or on an empty stomach.
authors.affiliation: Clinical Pharmacology Research Center, Department of Adult and Pediatric Medicine, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326, USA.
authors.forename: Allison W
authors.initials: AW
authors.lastname: Wallace
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Victory
authors.forename: Guy W
authors.initials: GW
authors.lastname: Amsden
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D001628:Beverages; D002118:Calcium; D032084:Citrus sinensis; D005260:Female; D024841:Fluoroquinolones; D005527:Food, Fortified; D018565:Food-Drug Interactions; D000077734:Gatifloxacin; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D002118:Calcium