Burstein A H, Gal P, Forrest A
Department of Pharmacy Practice and Science, University of Maryland at Baltimore 21201, USA.
Ann Pharmacother. 1997 Sep;31(9):980-3. doi: 10.1177/106002809703100904.
To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates.
Unblinded evaluation in neonates with presumed sepsis.
Level 3 community-based neonatal intensive care unit.
Eleven neonates with presumed sepsis.
Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose.
A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined.
For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.
运用最优抽样理论确定计算新生儿万古霉素药代动力学参数所需的最少万古霉素浓度数量及合适的采样时间。
对疑似脓毒症的新生儿进行非盲法评估。
基于社区的三级新生儿重症监护病房。
11例疑似脓毒症的新生儿。
给予12个疗程的静脉注射万古霉素，剂量为20mg/kg。在首剂1小时输注开始后3小时和9小时采集血样。
采用迭代两阶段分析法将二室模型拟合至万古霉素浓度。药代动力学参数估计值用于确定两样本、三样本和四样本策略的最优采样时间，随后生成100例病例的两样本、三样本和四样本浓度数据。通过计算和比较所确定策略的D效率来比较各策略的相对性能。确定100例模拟病例中各策略药代动力学参数估计值的偏差（中位百分比误差）和精密度（中位绝对百分比误差）。
对于估计中央室和外周室的总清除率和容积，所有策略表现相似，估计效率、偏差和精密度均无差异。我们的结果表明，对于临床评估，两个采样时间合适的样本（1小时输注后0.5小时，谷浓度）足以估计新生儿万古霉素清除率。
