Circadian changes in pharmacokinetics of sulfamethoxazole administered orally to rabbits

Circadian variations of sulfamethoxazole pharmacokinetics were studied after a single oral administration of sulfamethoxazole, 50 mg/kg, to rabbits at 09:00 (a.m.) and 22:00 (p.m.). The profiles of plasma sulfamethoxazole concentration showed from 6h to 24 h significant statistical difference (p < 0.05) between 09:00 and 22:00. The half-life (t(1/2)) was significantly shorter in the morning (11.2 +/- 3.2 h) when compared to the nighttime (15.4 +/- 3.5 h) (p < 0.05). The AUC was significantly decreased in the morning (1325 +/- 264 mug/ml.h) than that in the nighttime (2059 +/- 379 mug/ml.h) (p < 0.05). Total body clearance (CLt) was significantly higher when sulfamethoxazole was given in the morning (6.65 +/- 0.23 ml/min) versus in the nighttime (4.28 +/- 0.20 ml/min) (p < 0.05).