A MULTIPLE-DOSE PHARMACOKINETIC INTERACTION STUDY BETWEEN DIDANOSINE (VIDEX®) AND CIPROFLOXACIN (CIPRO®) IN MALE SUBJECTS SEROPOSITIVE FOR HIV BUT ASYMPTOMATIC
✍ Scribed by CATHERINE A. KNUPP; RASHMI H. BARBHAIYA
- Book ID
- 102658047
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 508 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
The pharmacokinetics of didanosine and cipro¯oxacin 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 1 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 q12h) for 3 d, followed by didanosine (200 mg q12h) and cipro¯oxacin (750 mg q12h) for 3 d, and ®nished with another course of didanosine (200 mg q12h for 3 d). Group B began with cipro¯oxacin, followed by the combination, and ®nished with cipro¯oxacin using the same doses and schedule as utilized in group A. During the combination phase of the study, cipro¯oxacin 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 cipro¯oxacin using validated HPLC methods. The plasma and urine data were subjected to noncompartmental pharmacokinetic analysis. A statistically signi®cant decrease in the average AUC and UR values of cipro¯oxacin 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 signi®cant. The apparent decrease in the bioavailability of cipro¯oxacin 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, cipro¯oxacin did not alter the pharmacokinetics of didanosine. The data from the present study demonstrate that didanosine or cipro¯oxacin 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 cipro¯oxacin must be taken at least 2 h prior to didanosine to avoid a clinically signi®cant interaction with the antacids present in the didanosine formulation.