Koren G, Barker C, Bohn D, Kent G, Biggar W D
Crit Care Med. 1985 Oct;13(10):844-7. doi: 10.1097/00003246-198510000-00014.
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 degrees C) and again 1 wk later after the induction of controlled hypothermia (29 degrees C). During hypothermia, the elimination half-time for gentamicin was significantly prolonged (135 +/- 19 min at 37 degrees C vs. 187 +/- 7 min at 29 degrees 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.
在体温正常（37摄氏度）时静脉注射一剂庆大霉素和氨茶碱，一周后在诱导控制性低温（29摄氏度）后再次给药，研究低温对庆大霉素和氨茶碱药代动力学的影响。在低温期间，庆大霉素的消除半衰期显著延长（37摄氏度时为135±19分钟，29摄氏度时为187±7分钟），庆大霉素中央室容积（Vc）、庆大霉素分布容积（Vd）和庆大霉素总体清除率（TBC）均显著降低。低温与氨茶碱Vd和Vc的小幅但显著降低有关，但TBC无变化。在单独的实验中，低温诱导期间心输出量以温度依赖的方式下降。庆大霉素Vd和TBC的变化可能由心输出量的降低以及相关的肾小球滤过率降低来解释。本研究表明，肝提取率相对较低的氨茶碱的消除不受低温诱导的肝血流量减少的影响。
