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Chronobiological variations of indomethacin pharmacokinetic parameters in sheep
Author(s) -
Boggio J. C.,
Valtorta S. E.,
Sánchez S.,
Mckellar Q.
Publication year - 2001
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1046/j.1365-2885.2001.00338.x
Subject(s) - pharmacokinetics , circadian rhythm , high performance liquid chromatography , elimination rate constant , volume of distribution , distribution (mathematics) , half life , chemistry , chromatography , pharmacology , medicine , mathematics , mathematical analysis
Boggio, J. C., Valtorta, S. E., Sánchez, S., McKellar, Q. Chronobiological variations of indomethacin pharmacokinetic parameters in sheep. J. vet. Pharmacol. Therap. 24, 261–265. A two‐phase study to investigate the influence of administration time on pharmacokinetics of indomethacin in sheep was performed. In phase I, 12 animals were allocated to four groups, each corresponding to a different time: 08:00, 14:00, 20:00, 02:00 h. Sheep received an intravenous administration of 1 mg/kg indomethacin. In phase II, each group was administered indomethacin with a 12‐h difference compared to Phase I. The trial was performed in autumn, and animals were subjected to a natural light:dark cycle of 10:14 h. Blood samples were taken and processed by high performance liquid chromatography (HPLC) with ultraviolet detection. For each pharmacokinetic parameter, an analysis of variance was performed to outline the existence of chronobiological variations. Concentration at zero time ( C 0 ), hybrid constant for distribution and its half life, hybrid constant for elimination and its half‐life, volume of distribution ( V d ), area under the curve ( AUC ∞ ) and clearance rate ( Cl ), presented chronobiological variations ( P < 0.05) and were fitted to a cosine equation. The following parameters adjusted to circadian rhythms: C 0 (acrophase: 13.9788 h); AUC ∞ (acrophase: 13.4377 h); V d (acrophase: 0.8245 h) and Cl (acrophase: 1.4965 h). It was concluded that pharmacokinetic parameters of intravenously injected indomethacin in sheep would behave in a different, though predictable, manner according to the animal’s biological clock.