DISPOSITION OF DIDANOSINE IN HIV-SEROPOSITIVE PATIENTS WITH NORMAL RENAL-FUNCTION OR CHRONIC-RENAL-FAILURE - INFLUENCE OF HEMODIALYSIS AND CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS

Objective: To evaluate the pharmacokinetics of didanosine in patients with normal kidney function or chronic kidney failure, Methods: Three groups of patients with human immunodeficiency virus (HIV) infection w ere studied: group I, six men with normal kidney function (creatinine clearance >90 ml/min/1.73 m(2)); group II, six men with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) ; and group III, four men and two women with chronic renal failure rec eiving hemodialysis three times a week. A 300 mg dose of didanosine wa s administered orally and intravenously according to a two-period rand omized crossover design. Patients in group III were studied between he modialysis sessions during the crossover periods, In addition, patient s in group m were studied in a third period after administration of a 300 mg oral dose of didanosine 4 hours before hemodialysis. Results: A fter intravenous administration in group I, the mean (+/-SD) total cle arance (CL,) was 13.0 +/- 1.6 ml/min/kg and the elimination half-life (t(1/2)) was 1.56 +/- 0.43 hour. In groups II and m, the CL(T) decreas ed significantly to 3.4 +/- 1.2 and 3.2 +/- 1.2 ml/min/kg, respectivel y, whereas the t(1/2) increased to 3.60 +/- 0.82 hours and 3.11 +/- 0. 88 hours, respectively, The absolute bioavailability of didanosine in groups I, II, and m was 42% +/- 12%, 52% +/- 6%, and 38% +/- 11%, resp ectively, and did not differ significantly, CAPD had Little effect on the removal of didanosine, whereas approximately 30% of the drug prese nt in the body at the start of dialysis was eliminated by an average a -hour dialysis session, Conclusion: The clearance of didanosine is imp aired in patients with chronic renal failure. To compensate, the dose and schedule of administration should be adjusted. It is recommended t hat one-fourth of the total daily dose of didanosine be administered o nce a day in this patient population.