Chronokinetics of active biliary ampicillin secretion in rats.
The existence of temporal variation in biliary excretion has been demonstrated for dibromosulfophthalein and ampicillin (AMP). This study was performed to investigate if the 24 h rhythm of active AMP biliary secretion could be attributed to circadian rhythms in the capacity and/or binding affinity of the active secretion mechanism. In this study, 12 Sprague-Dawley rats, housed under a 12 h light/12 h dark environment, were used. Each rat received four 1 h infusions of incremental doses of AMP during either the active (24:00 group) or rest phase (12:00 group) under pentobarbital anesthesia. High doses of AMP were administered to saturate the biliary secretion of AMP via the anion carrier system. Bile and plasma were collected at steady state for each infusion and analyzed by a microbiological assay. The systemic clearance of AMP was increased approximately twofold during the active phase (24:00 group) compared to the resting phase (12:00 group). Plots of bile excretion rate versus plasma concentration indicated saturation of the anion carrier system. Analysis of the data using the Michaelis-Menten model revealed no significant difference in the binding affinity (1/Km) of the biliary anion carrier system between the 12:00 and 24:00 groups. However, the maximum AMP excretion rate attained in the bile (maximum transport or Vmax) showed a 50% increase during the active phase, thus implicating a day-night variation in transport capacity of the anionic pathway. Therefore, temporal variation in the capacity of the secretory mechanisms is a determinant contributor to the proposed circadian rhythm observed in the biliary elimination of AMP.
University of Georgia, Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, Athens 30602-2353, USA.
B
B
Mesnard-Ricci
C A
CA
White
D000667:Ampicillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D007263:Infusions, Parenteral; D008297:Male; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010406:Penicillins; D000667:Ampicillin