title: Pharmacokinetics of azathioprine after repeated oral and single intravenous administration.
abstract: The pharmacokinetics of azathioprine (AZN) were examined in 28 renal transplant patients treated orally with 25 to 150 mg AZN once daily in combination with cyclosporin A and prednisone, and after single intravenous (IV) injection of 5 mg/kg AZN using the rabbit as an in vivo model. The steady-state concentrations of AZN observed in these patients ranged from 6 to 583 micrograms/L, and the interday coefficients of variation of the concentration in three randomly selected patients were 38%, 12%, and 4.6%. The frequency distribution pattern of the apparent oral clearance (TCLor) of AZN separates the patients almost equally into poor (TCLor = 0.126 to 4 L/hour.kg) and extensive metabolizers (TCLor = 5 to 12 L/hour.kg). The data obtained from the IV administration displayed the two-compartment model characteristics with mean (standard error of the mean) of alpha, beta, Vc, and total body clearance of 15.3 (2)/hour, 2.38 (.64)/hour, 1.05 (.3) L/kg, and 8.12 (1.26) L/hour.kg, respectively. The large variability in the pharmacokinetic parameters of AZN in patients and even in rabbits under carefully controlled conditions that may be ascribed to the complexity of its metabolism necessitates a careful approach to its dose selection.
authors.affiliation: Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: el-Yazigi
authors.forename: F A
authors.initials: FA
authors.lastname: Wahab
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D001379:Azathioprine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011817:Rabbits
chemical_list: D001379:Azathioprine