INTENSITY-DEPENDENT EFFECTS OF ACUTE SUBMAXIMAL EXERCISE ON THE PHARMACOKINETICS OF BROMSULPHALEIN IN HORSES

Objective-To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several subma ximal exercise intensities. Animals-8 adult Standardbred mares. Proced ure-Horses were subjected to 4 submaximal exercise intensities (restin g and 40, 60, and 80% maximal oxygen consumption). After horses had be en running at the required treadmill speed for ? minute, bromsulphalei n (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 6 0-second period, and horses continued at the desired speed for an addi tional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spec trophotometry. Estimates of pharmacokinetic variables were compared, a mong the 4 exercise intensities, using a Friedman repeated-measures an alysis on ranks and linear regression. Results-Median values fdr clear ance of BSP from blood and plasma decreased significantly with exercis e and was linearly related to exercise intensity. Exercise-induced dif ferences were not detected in the volume of distribution of BSP. Elimi nation half-life of BSP increased significantly with increasing exerci se intensity and was linearly related to exercise intensity. Conclusio ns-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 BS P and leading to persistence of plasma concentrations of BSP. Clinical Implications-Drugs that are efficiently extracted by the liver may ha ve decreased hepatic clearance when horses exercise at submaximal inte nsities.