Sulfadiazine handling in the rabbit. I. Pseudosaturation of N-acetyltransferase
Du Souich, P.; McLean, A.J.; Lalka, D.; Jenkins, B.; Haegele, K.D.; McNay, J.L.
Journal of Pharmacology and Experimental Therapeutics 207(1): 221-227
1978
ISSN/ISBN: 0022-3565 PMID: 702343 Document Number: 137116
The saturability of the N-acetyltransferase system was studied in groups of slow and fast acetylator rabbits. Both groups received 3 i.v. bolus doses of sulfadiazine (SDZ): 20, 40 and 80 mg/kg. SDZ and N-acetylsulfadiazine (NSDZ) were determined spectrophotometrically in sequential plasma samples taken over 4 h and in a 48-h collection of urine. Pharmacokinetic parameters derived by conventional techniques included area under the plasma time concentration curve (AUC), elimination half-life, apparent volume of distribution and apparent renal clearance. The AUC for SDZ when corrected for administered dose remained constant over the administered range of doses, while the corrected AUC of NSDZ decreased with increasing dose of SDZ. These observations were consistent with saturability of the M-acetyltransferase pathway. The percentage of administered SDZ dose recovered in urine as NSDZ remained constant over the range of SDZ doses. NSDZ apparent renal clearance increased with administered dose of SDZ. This pattern of metabolite disposition by the kidney was confirmed after i.v. administration of 10, 20 and 40 mg/kg of NSDZ. The acetylation of SDZ is not a saturable process in the rabbit.