Lack of bioequivalence of gatifloxacin when coadministered with calcium-fortified orange juice in healthy volunteers.

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.

RCT Entities:   Population Interventions Outcomes