BACKGROUND Morphine and hydromorphone have differing onsets, magnitudes, and durations of effects and side-effects. Differences between opioids in their interindividual variabilities in pharmacokinetics and pharmacodynamics might influence rational drug selection. Crossover drug studies can provide more informative interindividual variability data than parallel group studies. Using data from a crossover study of i.v. morphine and hydromorphone in healthy volunteers, we tested the hypothesis that morphine and hydromorphone differ in their interindividual pharmacokinetic variability. METHODS Arterial opioid and metabolite concentrations from a randomised crossover study in 51 volunteers receiving a 2-h infusion of hydromorphone (0.05 or 0.1 mg kg-1 i.v.) or morphine (total 0.1 or 0.2 mg kg-1 i.v.) 1-2 weeks apart were evaluated with a three-compartmental model for parent opioid and incorporating glucuronides using population modelling (NONMEM). The primary outcome was interindividual variability in pharmacokinetics, based on the coefficient of variation (%CV) of individual model parameters, calculated as √[exp(ω2)-1]×100 where ω2 is the interindividual variability. RESULTS Data were analysed per drug and in a combined morphine-hydromorphone model. Both analyses indicate that interindividual variabilities for hydromorphone and morphine were comparable with %CV ranging from 9% to 31% for structural model parameters (combined analysis). Similarly, additive and relative residual errors had comparable variabilities, 20-40% and 72-87%, respectively, for morphine and hydromorphone (combined analysis). CONCLUSIONS Morphine and hydromorphone did not differ in a statistically significant or clinically meaningful manner in their interindividual pharmacokinetic variability. Interindividual pharmacokinetic variability does not appear a meaningful consideration in the choice between these two opioids.

中文翻译：

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人类志愿者的吗啡和氢吗啡酮药代动力学：基于人群的个体间和阿片类药物相关变异性建模。


背景吗啡和氢吗啡酮具有不同的起效、幅度和效果和副作用的持续时间。阿片类药物之间在药代动力学和药效学的个体间差异可能会影响合理的药物选择。交叉药物研究可以提供比平行组研究更有用的个体间变异性数据。使用来自静脉注射吗啡和氢吗啡酮的交叉研究的数据 在健康志愿者中，我们检验了吗啡和氢吗啡酮在个体间药代动力学变异性上不同的假设。方法 来自一项随机交叉研究的动脉阿片类药物和代谢物浓度，该研究对 51 名志愿者进行 2 小时输注氢吗啡酮（0.05 或 0.1 mg kg-1 静脉注射）或吗啡（总共 0.1 或 0.2 mg kg-1 静脉注射）间隔 1-2 周，使用母体阿片类药物的三房模型和掺入葡萄糖醛酸酯使用群体模型 （NONMEM） 进行评估。主要结果是药代动力学的个体间变异性，基于单个模型参数的变异系数 （%CV），计算为 √[exp（ω2）-1]×100，其中 ω2 是个体间变异性。结果 对每种药物和吗啡-氢吗啡酮联合模型进行数据分析。两项分析都表明，氢吗啡酮和吗啡的个际变异性与结构模型参数的 %CV 相当（组合分析）在 9% 到 31% 之间。同样，吗啡和氢吗啡酮的加法误差和相对残差误差具有可比的变异性，分别为 20-40% 和 72-87%（联合分析）。结论吗啡和氢吗啡酮的个体间药代动力学变异性没有统计学意义或临床意义的差异。 在这两种阿片类药物之间进行选择时，个体间药代动力学变异性似乎不是一个有意义的考虑因素。