Chronokinetics of active biliary ampicillin secretion in rats. 1998

B Mesnard-Ricci, and C A White
University of Georgia, Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, Athens 30602-2353, USA.

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.

UI MeSH Term Description Entries
D007263 Infusions, Parenteral The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping. Intra-Abdominal Infusions,Intraperitoneal Infusions,Parenteral Infusions,Peritoneal Infusions,Infusion, Intra-Abdominal,Infusion, Intraperitoneal,Infusion, Parenteral,Infusion, Peritoneal,Infusions, Intra-Abdominal,Infusions, Intraperitoneal,Infusions, Peritoneal,Intra Abdominal Infusions,Intra-Abdominal Infusion,Intraperitoneal Infusion,Parenteral Infusion,Peritoneal Infusion
D008297 Male Males
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010406 Penicillins A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065) Antibiotics, Penicillin,Penicillin,Penicillin Antibiotics
D002940 Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Diurnal Rhythm,Nyctohemeral Rhythm,Twenty-Four Hour Rhythm,Nycthemeral Rhythm,Circadian Rhythms,Diurnal Rhythms,Nycthemeral Rhythms,Nyctohemeral Rhythms,Rhythm, Circadian,Rhythm, Diurnal,Rhythm, Nycthemeral,Rhythm, Nyctohemeral,Rhythm, Twenty-Four Hour,Rhythms, Circadian,Rhythms, Diurnal,Rhythms, Nycthemeral,Rhythms, Nyctohemeral,Rhythms, Twenty-Four Hour,Twenty Four Hour Rhythm,Twenty-Four Hour Rhythms
D000667 Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillin, Aminobenzyl,Amcill,Aminobenzylpenicillin,Ampicillin Sodium,Ampicillin Trihydrate,Antibiotic KS-R1,Omnipen,Pentrexyl,Polycillin,Ukapen,Aminobenzyl Penicillin,Antibiotic KS R1,KS-R1, Antibiotic,Sodium, Ampicillin,Trihydrate, Ampicillin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017711 Nonlinear Dynamics The study of systems which respond disproportionately (nonlinearly) to initial conditions or perturbing stimuli. Nonlinear systems may exhibit "chaos" which is classically characterized as sensitive dependence on initial conditions. Chaotic systems, while distinguished from more ordered periodic systems, are not random. When their behavior over time is appropriately displayed (in "phase space"), constraints are evident which are described by "strange attractors". Phase space representations of chaotic systems, or strange attractors, usually reveal fractal (FRACTALS) self-similarity across time scales. Natural, including biological, systems often display nonlinear dynamics and chaos. Chaos Theory,Models, Nonlinear,Non-linear Dynamics,Non-linear Models,Chaos Theories,Dynamics, Non-linear,Dynamics, Nonlinear,Model, Non-linear,Model, Nonlinear,Models, Non-linear,Non linear Dynamics,Non linear Models,Non-linear Dynamic,Non-linear Model,Nonlinear Dynamic,Nonlinear Model,Nonlinear Models,Theories, Chaos,Theory, Chaos

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