Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis.
The pharmacokinetics of didanosine were investigated following oral administration of a single 375-mg dose to eight human immunodeficiency virus-seropositive patients with normal renal function and eight human immunodeficiency virus-seropositive uremic patients. In uremic patients, the plasma half-life was longer than that in control patients (respectively, 4.5 +/- 2.2 and 1.6 +/- 0.4 h). The ratio of total plasma clearance to absolute bioavailability was four- to fivefold lower in uremic patients than in patients with normal renal function (respectively, 491 +/- 181 and 2,277 +/- 738 ml/min). Because of the decrease in elimination, concentrations in plasma were higher for uremic patients than for control patients; the maximum concentrations of drug in plasma were, respectively, 3,978 +/- 1,607 and 1,948 +/- 994 ng/ml; the areas under the concentration-time curve were, respectively, 14,050 +/- 4,262 and 3,000 +/- 956 ng.h/ml. Didanosine was removed by hemodialysis with an extraction ratio of 53% +/- 8%, a hemodialysis clearance value of 107 +/- 21 ml/min, and a fractional drug removal during a 4-h dialysis of 20% +/- 8% of the dose. Dosage adjustments are necessary in uremic patients.
Singlas
E
E
Hôpital Universitaire Bicêtre, Le Kremlin Bicetre, France.
Taburet
A M
AM
Borsa Lebas
F
F
Parent de Curzon
O
O
Sobel
A
A
Chauveau
P
P
Viron
B
B
al Khayat
R
R
Poignet
J L
JL
Mignon
F
F
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D016049:Didanosine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D014511:Uremia / Q000378:metabolism*
D016049:Didanosine