title: Chronopharmacokinetics of imipenem in the rat.
abstract: There are no studies indicating a possible modification of imipenem pharmacokinetics related to the hour (i.e., circadian time) of its administration. The aim of this study was to evaluate the influence of different times of intramuscular imipenem administration on its disposition in Wistar AF EOPS rats. Four groups of eight animals were given a single intramuscular injection of 140 mg/kg of imipenem either at 10:00, 16:00, 22:00, or 04:00 h. Blood samples were collected 0.5, 1, 2, 3, 4, 6, and 8 h after drug injection, and the main pharmacokinetic parameters determined were C(max), T(max), elimination half-life (t(1/2)), area under the concentration-versus-time curve (AUC), total serum clearance (CL/F), and volume of distribution (V/F). Circadian variation of C(max) (49%), T(max) (92%), and AUC (19%) was observed leading to variability of imipenem exposure. Clearance and volume of distribution were modified according to the circadian time of drug injection but did not reach statistical significance. The results suggest that varying the time of administration induces intra-individual variability.
authors.affiliation: Faculté de Médecine de Marseille, Laboratoire de Pharmacologie Médicale et Clinique, Université de la Méditerranée, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Boulamery
authors.forename: Gais
authors.initials: G
authors.lastname: Kadra
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simon
authors.forename: Thierry
authors.initials: T
authors.lastname: Besnard
authors.forename: Benard
authors.initials: B
authors.lastname: Bruguerolle
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002909:Chronobiology Phenomena; D019454:Chronotherapy; D002940:Circadian Rhythm / Q000502:physiology*; D015378:Imipenem / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem