Lavorini Federico, Geri Pietro, Camiciottoli Gianna, Pistolesi Massimo, Fontana Giovanni A
Dipartimento di Area Critica Medico Chirurgica, Unità Funzionale di Medicina Respiratoria, Università degli Studi di Firenze, Viale G B Morgagni 85-50134, Firenze, Italy.
Pulm Pharmacol Ther. 2008;21(2):380-4. doi: 10.1016/j.pupt.2007.10.001. Epub 2007 Oct 11.
For inhaled medications, bioequivalence testing is becoming increasingly important owing to the availability of many inhalation devices. We evaluated agreement between the Finney bioassay and the Emax model in the assessment of bioequivalence of salbutamol administered via a metered-dose inhaler with a spacer (pMDI+ Volumatic) or via a dry-powder inhaler (Diskus) in asthmatic patients with methacholine-induced bronchoconstriction. Eighteen patients inhaled methacholine until FEV 1 decreased by approximately 35% of control. Following inhalation of placebo, 200 and 400 mcg salbutamol through the pMDI+ Volumatic or the Diskus, changes in FEV 1 were repeatedly measured over a 60-min observation period. Bioequivalence of salbutamol administered via the two inhalation devices was assessed by calculating the relative potency of each device by using the Finney 2-by-2 parallel regression analysis and the non-linear, Emax model. Agreement between these methods in calculating relative potency was evaluated by using the Bland-Altman method. After salbutamol FEV 1 values were similar irrespective of the device employed, and greater (P<0.01) than those after placebo. However, assessment of relative potencies obtained with both the Finney (1.97, 90% CI 1.62-2.32) and the Emax (2.25, 90% CI 1.90-2.60) methods revealed that twice the salbutamol dose was needed to reverse methacholine-induced bronchoconstriction when the drug was inhaled via the Diskus than via the pMDI+ Volumatic. The mean difference in relative potency (-0.28, 90% CI -0.001 to -0.56) calculated with both methods did not significantly differ from zero, and none of the individual differences exceeded the limits of agreement. The Finney and the Emax methods provide comparable results in the evaluation of bioequivalence of different salbutamol formulations. The pMDI+ Volumatic is twice as efficient as the Diskus in lung delivery of salbutamol in asthma patients.
对于吸入药物，由于多种吸入装置的出现，生物等效性测试变得越来越重要。我们评估了在患有乙酰甲胆碱诱导支气管收缩的哮喘患者中，芬尼生物测定法和Emax模型在评估通过带储雾罐的定量吸入器（pMDI + Volumatic）或干粉吸入器（Diskus）给药的沙丁胺醇生物等效性方面的一致性。18名患者吸入乙酰甲胆碱直至第一秒用力呼气容积（FEV₁）下降约为对照值的35%。在吸入安慰剂、通过pMDI + Volumatic或Diskus吸入200和400微克沙丁胺醇后，在60分钟的观察期内反复测量FEV₁的变化。通过使用芬尼2×2平行回归分析和非线性Emax模型计算每种装置的相对效价，评估通过两种吸入装置给药的沙丁胺醇的生物等效性。使用布兰德 - 奥特曼方法评估这些方法在计算相对效价方面的一致性。吸入沙丁胺醇后，无论使用何种装置，FEV₁值相似，且比吸入安慰剂后更高（P<0.01）。然而，对通过芬尼方法（1.97，90%置信区间1.62 - 2.32）和Emax方法（2.25，90%置信区间1.90 - 2.60）获得的相对效价评估显示，当药物通过Diskus吸入时，逆转乙酰甲胆碱诱导的支气管收缩所需的沙丁胺醇剂量是通过pMDI + Volumatic吸入时的两倍。两种方法计算的相对效价的平均差异（-0.28，90%置信区间 -0.001至 -0.56）与零无显著差异，且个体差异均未超过一致性界限。芬尼方法和Emax方法在评估不同沙丁胺醇制剂的生物等效性方面提供了可比的结果。在哮喘患者中，pMDI + Volumatic在肺部递送沙丁胺醇方面的效率是Diskus的两倍。
