A multiple-dose pharmacokinetic interaction study between didanosine (Videx) and ciprofloxacin (Cipro) in male subjects seropositive for HIV but asymptomatic.
Author(s): Knupp CA, Barbhaiya RH
Affiliation(s): Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, USA.
Publication date & source: 1997-01, Biopharm Drug Dispos., 18(1):65-77.
Publication type: Clinical Trial; Randomized Controlled Trial
The pharmacokinetics of didanosine and ciprofloxacin were evaluated following the administration of multiple oral doses of each drug as a single agent or in combination. Didanosine was dosed as the Videx chewable/dispersible tablet, which contains the antacids dihydroxyaluminum sodium carbonate and magnesium hydroxide. Sixteen HIV-seropositive male subjects were randomly assigned to two groups of eight each. Group A received didanosine (200 mg q 12h) for 3d, followed by didanosine (200 mg q 12h) and ciprofloxacin (750 mg q 12h) for 3d, and finished with another course of didanosine (200 mg q 12h for 3 d). Group B began with ciprofloxacin, followed by the combination, and finished with ciprofloxacin using the same doses and schedule as utilized in group A. During the combination phase of the study, ciprofloxacin was administered 2 h prior to didanosine. Serial blood and urine samples were collected on study days 4, 8, and 12 for the quantitative determination of didanosine and ciprofloxacin using validated HPLC methods. The plasma and urine data were subjected to noncompartmental pharmacokinetic analysis. A statistically significant decrease in the average AUC and UR values of ciprofloxacin was noted when it was given with didanosine, relative to administration as a single agent. However, the magnitude of the decrease in these parameters, approximately 26 and 29%, respectively, was not considered clinically significant. The apparent decrease in the bioavailability of ciprofloxacin was probably due to the formation of a chelation complex between it and the aluminum- and magnesium-containing antacids found in the didanosine tablet. Other than an approximately 16% decrease in AUC, ciprofloxacin did not alter the pharmacokinetics of didanosine. The data from the present study demonstrate that didanosine or ciprofloxacin can be added to a treatment regimen consisting of the other single agent and that cessation of treatment with one agent does not have an impact on the pharmacokinetics of the other drug. The dose of ciprofloxacin must be taken at least 2h prior to didanosine to avoid a clinically significant interaction with the antacids present in the didanosine formulation.