Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex.
The pharmacokinetics of stavudine (d4T; 2',3'-didehydro-3'-deoxythymidine) were studied in patients with AIDS-related complex or AIDS enrolled in a dose-ranging phase I/II study. Twenty-two patients were studied after the first oral dose of 0.67, 1.33, 2.67, or 4 mg/kg of body weight; 17 of them underwent an additional steady-state pharmacokinetic evaluation after thrice-daily dosing of the above doses. Stavudine absorption was rapid, with mean peak concentrations of 1.2-4.2 mg/L over the four dose levels studied. From 34% to 41% of an oral dose was excreted as unchanged drug in the urine. The mean values for plasma elimination half-life ranged from 1 to 1.6 h. The absolute bioavailability of a 4 mg/kg oral dose exceeded 80%. There was no change in pharmacokinetic parameters measured after the first dose and after chronic dosing. Stavudine is a new dideoxynucleoside with more complete and less variable oral absorption than existing nucleosides used for treatment of human immunodeficiency virus infection.
Dudley
M N
MN
Antiinfective Pharmacology Research Unit, University of Rhode Island College of Pharmacy, Roger Williams Medical Center, Providence 02908.
Graham
K K
KK
Kaul
S
S
Geletko
S
S
Dunkle
L
L
Browne
M
M
Mayer
K
K
D000386:AIDS-Related Complex / Q000188:drug therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003710:Demography; D015224:Dideoxynucleosides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018119:Stavudine
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D018119:Stavudine