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 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.


CONCLUSIONS
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.
Knupp
C A
CA
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
Hak
L J
LJ
Coakley
D F
DF
Falk
R J
RJ
Wagner
B E
BE
Raasch
R H
RH
van der Horst
C M
CM
Kaul
S
S
Barbhaiya
R H
RH
Dukes
G E
GE
D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D003956:Dialysis; D016049:Didanosine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012016:Reference Values
D019380:Anti-HIV Agents; D016049:Didanosine