Intensity-dependent effects of acute submaximal exercise on the pharmacokinetics of bromsulphalein in horses

T. M. Dyke From the Analytical Toxicology Laboratory (Dyke, Sams) and the Exercise Physiology Laboratory (Hinchcliff), College of Veterinary Medicine, The Ohio State University, 610 Vernon L. Tharp St, Columbus, OH 43210-1089.

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R. A. Sams From the Analytical Toxicology Laboratory (Dyke, Sams) and the Exercise Physiology Laboratory (Hinchcliff), College of Veterinary Medicine, The Ohio State University, 610 Vernon L. Tharp St, Columbus, OH 43210-1089.

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K. W. Hinchcliff From the Analytical Toxicology Laboratory (Dyke, Sams) and the Exercise Physiology Laboratory (Hinchcliff), College of Veterinary Medicine, The Ohio State University, 610 Vernon L. Tharp St, Columbus, OH 43210-1089.

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Abstract

Objective

To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several submaximal exercise intensities.

Animals

8 adult Standardbred mares.

Procedure

Horses were subjected to 4 submaximal exercise intensities (resting and 40, 60, and 80% maximal oxygen consumption). After horses had been running at the required treadmill speed for 1 minute, bromsulphalein (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 60-second period, and horses continued at the desired speed for an additional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spectrophotometry. Estimates of pharmacokinetic variables were compared among the 4 exercise intensities, using a Friedman repeated-measures analysis on ranks and linear regression.

Results

Median values for clearance of BSP from blood and plasma decreased significantly with exercise and was linearly related to exercise intensity. Exercise-induced differences were not detected in the volume of distribution of BSP. Elimination half-life of BSP increased significantly with increasing exercise intensity and was linearly related to exercise intensity.

Conclusions

Acute submaximal exercise has a dramatic effect on clearance of BSP in horses. Presumably, exercise-induced decreases in splanchnic blood flow limit blood flow to the liver, decreasing hepatic clearance of BSP and leading to persistence of plasma concentrations of BSP.

Clinical Implications

Drugs that are efficiently extracted by the liver may have decreased hepatic clearance when horses exercise at submaximal intensities. (Am J Vet Res 1998;59:1481–1487)

Abstract

Objective

To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several submaximal exercise intensities.

Animals

8 adult Standardbred mares.

Procedure

Horses were subjected to 4 submaximal exercise intensities (resting and 40, 60, and 80% maximal oxygen consumption). After horses had been running at the required treadmill speed for 1 minute, bromsulphalein (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 60-second period, and horses continued at the desired speed for an additional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spectrophotometry. Estimates of pharmacokinetic variables were compared among the 4 exercise intensities, using a Friedman repeated-measures analysis on ranks and linear regression.

Results

Median values for clearance of BSP from blood and plasma decreased significantly with exercise and was linearly related to exercise intensity. Exercise-induced differences were not detected in the volume of distribution of BSP. Elimination half-life of BSP increased significantly with increasing exercise intensity and was linearly related to exercise intensity.

Conclusions

Acute submaximal exercise has a dramatic effect on clearance of BSP in horses. Presumably, exercise-induced decreases in splanchnic blood flow limit blood flow to the liver, decreasing hepatic clearance of BSP and leading to persistence of plasma concentrations of BSP.

Clinical Implications

Drugs that are efficiently extracted by the liver may have decreased hepatic clearance when horses exercise at submaximal intensities. (Am J Vet Res 1998;59:1481–1487)

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