Effects of Hypothermia on Drug Absorption

Abstract

The in situ rat gut technique was used to study the effects of hypothermia on the intestinal absorption of a 1 mg/ml solution of sodium pentobarbital in 0.01 M phosphate buffer (pH 6.0). Male Sprague-Dawley rats weighing between 300 and 370 g were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0–4°C for 5 hr. This procedure lowers the rectal temperature of the rats from 38 to 20°C. The animals were prepared for surgery using ether as anesthetic after their rectal temperature reached 20°C. Water flux in and out of the intestinal lumen was estimated from tritiated polyethylene glycol 4000 concentrations in the perfusate. The disappearance rate constant of pentobarbital from the intestinal lumen was 0.0638 ± 0.007 min⁻¹ for hypothermic rats, in comparison to 0.114 ± 0.0123 min⁻¹ for normothermic rats.