Department of Anesthesiology and Critical Care, Stellenbosch University, South Africa.
Clin Pharmacokinet. 2012 Mar 1;51(3):137-45. doi: 10.2165/11596980-000000000-00000.
Uncertainty exists as to the most suitable pharmacokinetic parameter sets for propofol target-controlled infusions (TCI). The pharmacokinetic parameter sets currently employed are clearly not universally applicable, particularly when patient attributes differ from those of the subjects who participated in the original research from which the models were derived. Increasing evidence indicates that the pharmacokinetic parameters of propofol can be scaled allometrically as well as in direct proportion to lean body mass (LBM). Appraisal of hitherto published studies suggests that an allometrically scaled pharmacokinetic parameter set may be applicable to a wide range of patients ranging from children to obese adults. On the other hand, there is evidence that propofol pharmacokinetic parameters, scaled linearly to LBM, provide improved dosing in normal and obese adults. The 'Schnider' pharmacokinetic parameter set that has been programmed into commercially available TCI pumps cannot be employed at present for morbidly obese patients (body mass index >40 kg/m2), because of anomalous behaviour of the equation used to calculate LBM, resulting in administration of excessive amounts of propofol. Simulations of TCI using improved equations to calculate LBM indicate that the Schnider model delivers similar amounts of propofol to morbidly obese patients as do the allometrically scaled pharmacokinetic parameter sets. These hypotheses deserve further investigation. To facilitate further investigation, researchers are encouraged to make their data freely available to the WorldSIVA Open TCI Initiative (http://opentci.org).
关于丙泊酚靶控输注(TCI)最合适的药代动力学参数集,目前仍存在不确定性。目前使用的药代动力学参数集显然不是普遍适用的,特别是当患者的特征与原始研究中模型推导所涉及的研究对象不同时。越来越多的证据表明,丙泊酚的药代动力学参数可以根据瘦体重(LBM)进行比例缩放和直接比例缩放。对迄今为止已发表的研究的评估表明,一种比例缩放的药代动力学参数集可能适用于从儿童到肥胖成年人的广泛患者群体。另一方面,有证据表明,按 LBM 线性缩放的丙泊酚药代动力学参数可改善正常和肥胖成年人的给药剂量。目前,由于用于计算 LBM 的方程的异常行为,无法在病态肥胖患者(体重指数>40kg/m2)中使用已编程到市售 TCI 泵中的“Schnider”药代动力学参数集,这会导致过量的丙泊酚给药。使用改进的方程计算 LBM 的 TCI 模拟表明,Schnider 模型向病态肥胖患者输送的丙泊酚量与比例缩放的药代动力学参数集相似。这些假设值得进一步研究。为了促进进一步研究,鼓励研究人员将其数据免费提供给 WorldSIVA Open TCI 倡议(http://opentci.org)。