Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: influence of hemodialysis and continuous ambulatory peritoneal dialysis

Clin Pharmacol Ther. 1996 Nov;60(5):535-42. doi: 10.1016/S0009-9236(96)90149-6.


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 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.

Results: 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Anti-HIV Agents / urine
  • Dialysis
  • Didanosine / administration & dosage
  • Didanosine / blood
  • Didanosine / pharmacokinetics*
  • Didanosine / urine
  • Female
  • HIV Seropositivity / metabolism*
  • Humans
  • Injections, Intravenous
  • Kidney / metabolism*
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Reference Values


  • Anti-HIV Agents
  • Didanosine