Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: Influence of hemodialysis and continuous ambulatory peritoneal dialysis*
- 19 November 1996
- journal article
- clinical trial
- Published by Wiley in Clinical Pharmacology & Therapeutics
- Vol. 60 (5) , 535-542
- https://doi.org/10.1016/s0009-9236(96)90149-6
Abstract
To evaluate the pharmacokinetics of didanosine in patients with normal kidney function or chronic kidney failure. Three groups of patients with human immunodeficiency virus (HIV) infection were studied: group I, six men with normal kidney function (creatinine clearance > 90 ml/min/1.73 m2); 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 receiving hemodialysis three times a week. A 300 mg dose of didanosine was administered orally and intravenously according to a two-period randomized crossover design. Patients in group III were studied between hemodialysis sessions during the crossover periods. In addition, patients in group III were studied in a third period after administration of a 300 mg oral dose of didanosine 4 hours before hemodialysis. After intravenous administration in group I, the mean (+/-SD) total clearance (CLT) 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 III, the CLT decreased significantly to 3.4 +/- 1.2 and 3.2 +/- 1.2 ml/min/kg, respectively, whereas the t1/2 increased to 3.60 +/- 0.82 hours and 3.11 +/- 0.88 hours, respectively. The absolute bioavailability of didanosine in groups I, II, and III was 42% +/- 12%, 52% +/- 6%, and 38% +/- 11%, respectively, and did not differ significantly. CAPD had little effect on the removal of didanosine, whereas approximately 30% of the drug present in the body at the start of dialysis was eliminated by an average 3-hour dialysis session. The clearance of didanosine is impaired in patients with chronic renal failure. To compensate, the dose and schedule of administration should be adjusted. It is recommended that one-fourth of the total daily dose of didanosine be administered once a day in this patient population.Keywords
This publication has 17 references indexed in Scilit:
- Purine metabolism in women with primary goutThe American Journal of Medicine, 1994
- Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysisAntimicrobial Agents and Chemotherapy, 1992
- Metabolism of 2′,3′-dideoxyinosine (ddI) in human blood.Published by Wiley ,1992
- Metabolism of 14C‐2′,3′‐dideoxyinosine by the in situ perfused rat liver preparationBiopharmaceutics & Drug Disposition, 1991
- Quantitation of didanosine in human plasma and urine by high-performance liquid chromatographyJournal of Chromatography B: Biomedical Sciences and Applications, 1990
- Initial studies on the cellular pharmacology of 2′,3′-dideoxyinosine, an inhibitor of HIV infectivityBiochemical Pharmacology, 1987
- Initial studies on the cellular pharmacology of 2',3'-dideoxyadenosine, an inhibitor of HTLV-III infectivityBiochemical Pharmacology, 1987
- Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro.Proceedings of the National Academy of Sciences, 1987
- Drug Therapy in Patients Undergoing HaemodialysisClinical Pharmacokinetics, 1984
- The assessment of fractional drug removal by extracorporeal dialysisBiopharmaceutics & Drug Disposition, 1982