Malan T P, Sameshima T, Mata H, Frink E J
Department of Anesthesiology, University of Arizona Health Sciences Center, Tucson 85724, USA.
Anesth Analg. 1995 Sep;81(3):576-80. doi: 10.1097/00000539-199509000-00027.
In patients, plasma concentrations of sevoflurane metabolites may be independent of inspired sevoflurane concentration over a defined dose range. In contrast, studies using rabbits have found that plasma concentrations and urinary excretion of fluoride ion are dose-dependent up to 3% inspired sevoflurane. We measured sevoflurane metabolite concentrations in adult male Sprague-Dawley rats and related them to inspired sevoflurane concentrations. When plasma concentrations and urinary excretion of metabolites were measured in vivo, they were dependent on inspired anesthetic concentration at concentrations less than 1.25%, but became less dose-dependent at higher anesthetic concentrations. Sevoflurane metabolism by precision-cut liver slices in vitro became dose-independent at more than 10-30 microM sevoflurane. No evidence of substrate inhibition was observed. These data provide evidence that sevoflurane metabolite concentrations are almost independent of inspired anesthetic concentration over at least part of the clinically used concentration range.
在患者中，在规定的剂量范围内，七氟醚代谢物的血浆浓度可能与吸入的七氟醚浓度无关。相比之下，对兔子的研究发现，在吸入七氟醚达3%时，氟离子的血浆浓度和尿排泄量呈剂量依赖性。我们测量了成年雄性Sprague-Dawley大鼠体内七氟醚代谢物的浓度，并将其与吸入的七氟醚浓度相关联。当在体内测量代谢物的血浆浓度和尿排泄量时，在浓度低于1.25%时，它们依赖于吸入麻醉剂浓度，但在较高麻醉剂浓度时剂量依赖性降低。体外精密肝切片对七氟醚的代谢在七氟醚浓度超过10 - 30微摩尔时变为非剂量依赖性。未观察到底物抑制的证据。这些数据表明，在至少部分临床使用的浓度范围内，七氟醚代谢物浓度几乎与吸入麻醉剂浓度无关。
