Pharmacokinetics of caffeine in lactating dairy cows

F. J. DeGraves From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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D. C. Ruffin From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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S. H. Duran From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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J. S. Spano From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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E. M. Whatley From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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J. Schumacher From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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M. G. Riddell From the Departments of Large Animal Surgery and Medicine (DeGraves, Ruffin, Duran, Schumacher, RiddeU) and Pathobiology (Spano, Whatley), College of Vetennary Medicine, Auburn University, Auburn, AL 36849-5522

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SUMMARY

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after IV administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 μg/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.

SUMMARY

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after IV administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 μg/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.

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