Pharmacokinetics of caffeine in the oestrogen-implanted ovariectomized ewe.
The disposition kinetics of caffeine and its metabolites theophylline, theobromine 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.
Pollard
I
I
School of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia.
Williamson
S
S
Downing
J
J
Scaramuzzi
R
R
D000818:Animals; D019540:Area Under Curve; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage*; D004973:Estrus Synchronization; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D010052:Ovariectomy / Q000662:veterinary; D012756:Sheep; D013805:Theobromine / Q000097:blood / Q000493:pharmacokinetics; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics
D000697:Central Nervous System Stimulants; D004343:Drug Implants; D002110:Caffeine; D004958:Estradiol; D013806:Theophylline; D013805:Theobromine; C021183:1,7-dimethylxanthine