A SHEEP PREPARATION FOR STUDYING INTERACTIONS BETWEEN BLOOD FLOW AND DRUG DISPOSITION.

Abstract

Control measurements of bloodflow through and cefoxitin extraction ratios across heart and lungs, liver, kidneys and gut were made under steadystate conditions in awake unrestrained sheep. The studies then were repeated with the same animals anaesthetized with 1.5% halothane or whilst undergoing high thoracic (to approximately 74) subarachnoid blockade with amethocaine. In the control-drug studies, it was shown that cefoxitin was cleared by the kidneys and that the cefoxitin infusion produced no significant changes in haemodynamics or in the kinetics of iodohippurate (the marker substance used for determining renal blood flow). Under general anaesthesia, there were significant reductions in renal blood flow (to 61% of the mean control value), in iodohippurate renal extraction ratio and clearance (to, respectively, 64 and 38% of the mean control values) and in cefoxitin renal extraction ratio and clearance (to, respectively, 48 and 23% of the mean control values). Under spinal anaesthesia there were no significant changes in haemodynamics or in cefoxitin or iodohippurate extraction ratios or clearances.