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Pharmacokinetics of caffeine in the oestrogen‐implanted ovariectomized ewe
Author(s) -
POLLARD IRINA,
WILLIAMSON SUSAN,
DOWNING JEFF,
SCARAMUZZI REX
Publication year - 1996
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 - 10.1111/j.1365-2885.1996.tb00022.x
Subject(s) - caffeine , paraxanthine , theophylline , pharmacokinetics , ovariectomized rat , context (archaeology) , metabolite , chemistry , pharmacology , endocrinology , area under the curve , medicine , metabolism , hormone , biology , cyp1a2 , paleontology , cytochrome p450
The disposition kinetics of caffeine and its metabolites theophylline, theobro‐mine and paraxanthine in the oestrogen‐implanted ovariectomized ewe following single intravenous doses of 5, 10, 15 or 20 mg/kg caffeine are described in this paper. Blood was collected at 5, 30 and 60 min, and at 3, 6, 8, 12, 24, 48, 72, 96, 120, 144, 192 and 240 h after dosing. Caffeine concentrations peaked within 30 min of administration but remained in a plateau phase for 3‐6 h before declining over a prolonged period of time. For caffeine the mean elimination half‐life was calculated to be 47 h. Detectable caffeine concentrations remained for 10 days after administration in all groups. The area under the plasma concentration‐time curve ( AUC ) values were used to compare tissue caffeine exposure and were, approximately, linearly related to dose. Metabolite concentrations were maintained at peak and near peak concentrations for 6‐24 h after caffeine administration followed by prolonged elimination. Because of significant species differences in drug elimination rates, it is concluded that the ewe is not a suitable animal model in the clinical context. However, the sheep may well provide insights into caffeine's mechanism of action of relevance to veterinary drug research.