Influence of hypothermia on the pharmacokinetics of gentamicin and theophylline in piglets

The influence of hypothermia on gentamicin and theophylline pharmacokinetics was studied in anesthetized pigs given an iv bolus of gentamicin and theophylline during normothermia (37°C) and again 1 wk later after the induction of controlled hypotherma (29°C). During hypothermia, the elimination half-time for gentamicin was significantly prolonged (135 ± 19 min at 37°C vs. 187 ± 7 min at 29°C), and there were significant decreases in the volume of the central compartment (Vc) of gentamicin, the gentamicin volume of distribution (Vd), and the gentamicin total body clearance (TBC). Hypothermia was associated with a small but significant decrease in theophylline Vd and Vc, but no change in TBC. In separate experiments, cardiac output decreased during the induction of hypothermia in a temperature-dependent fashion. The changes in gentamicin Vd and TBC may be explained by the decrease in cardiac output and the associated decrease in glomerular filtration rate. This study suggests that the elimination of theophylline, which has a relatively low hepatic extraction ratio, is not influenced by the hypothermia-induced decrease in liver blood flow.