COMPARISON OF THE PLASMA PHARMACOKINETICS AND RENAL CLEARANCE OF DIDANOSINE DURING ONCE AND TWICE-DAILY DOSING IN HIV-1-INFECTED INDIVIDUALS

Objective: To compare the plasma pharmacokinetics of didanosine during once daily (qd) and twice daily (bid) dosing. Design: Open-label, ran domized, cross-over study. Methods: HIV-1 infected patients who used d idanosine were randomized to either a qd or a bid dosing regimen of di danosine. The total daily dose of didanosine was identical in both reg imens. Seven days after the start of the study, the pharmacokinetic pr ofile of didanosine in plasma and urine was assessed during an 8-h per iod. The next day, the patient was switched to the opposite dosing reg imen, and after another 7 days, the study was concluded by again asses sing the plasma and urine pharmacokinetics of didanosine during 8 h. R esults: A total of 19 patients completed the study. The pharmacokineti cs of didanosine in plasma (with maximum plasma concentration adjusted for dose) and urine were not significantly different in the qd and bi d dosing regimen (P greater than or equal to 0.28 for all parameters). Conclusion: We conclude that qd dosing of didanosine leads to a simil ar exposure in plasma as bid dosing (using the same total daily dose). Since qd dosing may lead to improved compliance of patients to regime ns containing didanosine, these results provide a rationale for prescr ibing didanosine in a qd regimen, and is reassuring when we realize th at the drug is being administered in a qd dosing regimen on a large sc ale in clinical practice.