Continuous measurement of caffeine and two metabolites in blood and skeletal muscle of unrestrained adult horses by semi-automated in vivo microdialysis.
Concentrations of caffeine (CA) and two metabolites were measured simultaneously in venous blood and splenius muscle of adult horses using a semi-automated in vivo microdialysis sampling technique. Dialysates from muscle and jugular vein were collected continuously for 48 h and drug levels were determined by high performance liquid chromatography (HPLC). Following i.v. injection, CA (3 mg/kg) attained a peak blood level of nearly 5400 +/- 600 ng/mL and decreased with a half-life of 15.3 +/- 0.7 h. Pharmacokinetic and statistical comparisons between CA concentrations in jugular dialysates and plasma samples revealed no significant differences between these sampling techniques. However, measurements in muscle and blood revealed unexpected pharmacokinetic differences, including significantly elevated concentrations of CA in muscle for 4 h following drug administration. In contrast, the CA metabolites theophylline (TP) and theobromine (TB) exhibited delayed appearances in muscle and blood with peak concentrations of 300 +/- 60 ng/mL (TP) and 150 +/- 50 ng/mL (TB) detected in both tissues 1 day following CA administration. This study demonstrates that our novel semi-automated microdialysis procedure for continuous monitoring of drug and metabolite levels may be useful for related studies in other domesticated large animal species.
Chou
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CC
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610-0144, USA.
Webb
A I
AI
Brown
M P
MP
Gronwall
R R
RR
Vickroy
T W
TW
D000818:Animals; D019540:Area Under Curve; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D000697:Central Nervous System Stimulants / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005260:Female; D006736:Horses / Q000378:metabolism*; D007275:Injections, Intravenous / Q000662:veterinary; D017551:Microdialysis / Q000295:instrumentation / Q000592:standards / Q000662:veterinary*; D018482:Muscle, Skeletal / Q000378:metabolism*; D015203:Reproducibility of Results; D013805:Theobromine / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism
D000697:Central Nervous System Stimulants; D002110:Caffeine; D013806:Theophylline; D013805:Theobromine