Lum B L, Tam J, Kaubisch S, Flechner S M
Department of Pharmacy Practice, University of the Pacific at the Veterans Affairs Medical Center, Palo Alto, California.
J Clin Pharmacol. 1992 Oct;32(10):911-4. doi: 10.1002/j.1552-4604.1992.tb04637.x.
The harmonic and arithmetic mean values for volume of distribution at steady state, half-life, and clearance of intravenous cyclosporin-A were calculated using an index set of 22 renal transplant candidates to determine if harmonic mean values provide a less biased estimate of central tendency than arithmetic mean values. Cyclosporin-A was measured using a nonspecific radioimmune assay method. The arithmetic mean value for volume of distribution was 16% larger than calculations by the harmonic mean method. Similarly, the arithmetic mean half-life and clearance values were larger than harmonic mean values by 10% and 15%, respectively. However, 95% confidence intervals for these pharmacokinetic parameters overlapped. When these mean pharmacokinetic parameter values were used to predict actual values in a test group of 22 renal transplant candidates receiving cyclosporin-A, similar levels of precision were demonstrated by either method. Both methods produced positively biased predictions for volume of distribution and clearance. However, these differences were not significant. These findings suggest there is little practical value for the use of harmonic mean calculations to describe the central tendency of pharmacokinetic parameters of cyclosporin-A under the conditions studied. The value of harmonic mean values for pharmacokinetic parameters in other patient populations or with other assay methods for cyclosporin remain to be studied.
使用22名肾移植候选者的指标集计算静脉注射环孢素A的稳态分布容积、半衰期和清除率的调和均值与算术均值，以确定调和均值是否比算术均值能提供偏差更小的集中趋势估计值。环孢素A采用非特异性放射免疫分析法测定。分布容积的算术均值比调和均值法计算的值大16%。同样，算术平均半衰期和清除率值分别比调和均值大10%和15%。然而，这些药代动力学参数的95%置信区间相互重叠。当使用这些平均药代动力学参数值预测22名接受环孢素A治疗的肾移植候选者测试组中的实际值时，两种方法显示出相似的精度水平。两种方法对分布容积和清除率的预测均产生正偏差。然而，这些差异并不显著。这些发现表明，在所研究的条件下，使用调和均值计算来描述环孢素A药代动力学参数的集中趋势几乎没有实际价值。环孢素在其他患者群体中的药代动力学参数调和均值的价值或使用其他环孢素测定方法的情况仍有待研究。
