Application of an enzyme-multiplied immunoassay technique for determination of caffeine elimination kinetics as a test of liver function in clinically normal dogs

Dennis L. Golden From the Departments of Small Animal Surgery and Medicine (Golden), Pathobiology (Spano, Whatley), Physiology and Pharmacology (Wilson), and Large Animal Surgery and Medicine (DeGraves), College of Veterinary Medicine, Auburn University, AL 36849-5523.

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Joseph S. Spano From the Departments of Small Animal Surgery and Medicine (Golden), Pathobiology (Spano, Whatley), Physiology and Pharmacology (Wilson), and Large Animal Surgery and Medicine (DeGraves), College of Veterinary Medicine, Auburn University, AL 36849-5523.

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Robert C. Wilson From the Departments of Small Animal Surgery and Medicine (Golden), Pathobiology (Spano, Whatley), Physiology and Pharmacology (Wilson), and Large Animal Surgery and Medicine (DeGraves), College of Veterinary Medicine, Auburn University, AL 36849-5523.

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Fred J. DeGraves From the Departments of Small Animal Surgery and Medicine (Golden), Pathobiology (Spano, Whatley), Physiology and Pharmacology (Wilson), and Large Animal Surgery and Medicine (DeGraves), College of Veterinary Medicine, Auburn University, AL 36849-5523.

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Elizabeth M. Whatley From the Departments of Small Animal Surgery and Medicine (Golden), Pathobiology (Spano, Whatley), Physiology and Pharmacology (Wilson), and Large Animal Surgery and Medicine (DeGraves), College of Veterinary Medicine, Auburn University, AL 36849-5523.

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Summary

A commercially available automated enzyme-multiplied immunoassay technique (emit) was used to determine serum caffeine concentration after oral and iv administrations of caffeine at dosage of 5 mg/kg of body weight to 12 clinically normal dogs. Dogs were allotted to 2 groups of 6 dogs each; 1 group initially received caffeine orally and the other received caffeine iv. After 72 hours, caffeine administration was repeated in all dogs in the alternate manner. Serum samples were obtained at multiple intervals over 24 hours to determine distribution and elimination kinetics. Analysis of the drug concentration-time data indicated iv elimination half-life (t½) of 6.39 ± 1.87 hours, volume of distribution at steady state of 685.3 ± 132.2 ml/kg, total body clearance of 1.31 ± 0.38 ml/min/kg, absorption t½ of 1.02 ± 0.68 hour, oral elimination t½ of 6.53 ± 2.72 hours, lag time after oral administration of 0.0614 ± 0.0661 hour, highest measured concentration of 5.29 ± 1.17 μg/ml, time to peak concentration of 2.74 ± 1.30 hours, and bioavailability of 99.4 ± 19.4%. Data from 6 dogs best fit a 1-compartment open model and those from 6 other dogs best fit a 2-compartment open model. On the basis of data from the 6 dogs that best fit a 2-compartment model, t½ of distribution was 0.58 ± 0.72 hour. Data for oral administration best fit a single absorption phase and a single elimination phase.

The increased availability and simplicity of the emit offers an opportunity to study the application of caffeine elimination for clinical evaluation of dogs with liver disease. Data obtained from this study allow determination of t½ and clearance to be simplified by obtaining samples 4 and 8 hours after oral or iv administrations and establishes canine reference values for elimination kinetics of caffeine administered at dosage of 5 mg/kg and assayed by use of the emit.

Summary

A commercially available automated enzyme-multiplied immunoassay technique (emit) was used to determine serum caffeine concentration after oral and iv administrations of caffeine at dosage of 5 mg/kg of body weight to 12 clinically normal dogs. Dogs were allotted to 2 groups of 6 dogs each; 1 group initially received caffeine orally and the other received caffeine iv. After 72 hours, caffeine administration was repeated in all dogs in the alternate manner. Serum samples were obtained at multiple intervals over 24 hours to determine distribution and elimination kinetics. Analysis of the drug concentration-time data indicated iv elimination half-life (t½) of 6.39 ± 1.87 hours, volume of distribution at steady state of 685.3 ± 132.2 ml/kg, total body clearance of 1.31 ± 0.38 ml/min/kg, absorption t½ of 1.02 ± 0.68 hour, oral elimination t½ of 6.53 ± 2.72 hours, lag time after oral administration of 0.0614 ± 0.0661 hour, highest measured concentration of 5.29 ± 1.17 μg/ml, time to peak concentration of 2.74 ± 1.30 hours, and bioavailability of 99.4 ± 19.4%. Data from 6 dogs best fit a 1-compartment open model and those from 6 other dogs best fit a 2-compartment open model. On the basis of data from the 6 dogs that best fit a 2-compartment model, t½ of distribution was 0.58 ± 0.72 hour. Data for oral administration best fit a single absorption phase and a single elimination phase.

The increased availability and simplicity of the emit offers an opportunity to study the application of caffeine elimination for clinical evaluation of dogs with liver disease. Data obtained from this study allow determination of t½ and clearance to be simplified by obtaining samples 4 and 8 hours after oral or iv administrations and establishes canine reference values for elimination kinetics of caffeine administered at dosage of 5 mg/kg and assayed by use of the emit.

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