酚妥拉明生物等效性研究。

Phentolamine bioequivalence study.

作者信息

Silva L F G, Moraes M O, Santana G S M, Frota Bezerra F A, De Nucci G, Moraes M E A

机构信息

Urology, Clinical Pharmacology Unit (UNIFAC), Federal University of Ceara, Brazil.

出版信息

Int J Clin Pharmacol Ther. 2004 Jan;42(1):43-9.

PMID:14756387

Abstract

OBJECTIVE

To assess the bioequivalence of 2 tablet formulations of phentolamine (Regitine phentolamine 40 mg tablet formulation by Novartis, Brazil, as test formulation, and Vasomax, phentolamine 40 mg tablet formulation by Schering Plough S.A., Brazil, as reference formulation).

METHODS

A single 40 mg oral dose of each formulation was administered to 36 male healthy volunteers. The study was conducted after screening, using an open, randomized, 2-period crossover design, a 7-day interval between doses, and wash-out period of at least 4 weeks. Plasma samples for determination of phentolamine were obtained predose and at intervals over 720 min postdose. Plasma concentrations were quantified by reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM) method. Precision of the method was evaluated using calibration curves and plasma quality control samples. The subjects were monitored throughout the study. Systolic and diastolic blood pressure and pulse rate measurement were taken predose and at intervals up to 720 min. Tolerance of both products was good. No serious adverse reactions were reported. The pharmacokinetic parameters calculated for both compounds included: AUC(0-720 min), AUC(0-infinity), C(max), Ca and k(e).

RESULTS

The maximum concentrations reached (C(max)) were compared. Regitine 40 mg formulation C(max) geometric mean ratio was 108.29% (90% CI = 98.58-118.96) of Vasomax 40 mg formulation. The areas under the curve (AUC(0-720 min)) were compared. Regitine 40 formulation (AUC(0-720 min)) geometric mean ratio was 102.33% (90% CI = 97.21-107.72) of Vasomax 40 mg formulation.

CONCLUSION

Since the 90% CI for both C(max) and AUC ratio where inside the 80 to 125% interval proposed by the Food and Drug Administration, it is concluded that Regitine 40 mg tablet is bioequivalent to Vasomax for the rate and extent of absorption.

摘要

目的

评估两种酚妥拉明片剂剂型（巴西诺华公司生产的Regitine酚妥拉明40毫克片剂剂型作为试验制剂，以及巴西先灵葆雅公司生产的Vasomax酚妥拉明40毫克片剂剂型作为参比制剂）的生物等效性。

方法

对36名男性健康志愿者单次口服给予每种制剂40毫克。在筛选后进行该研究，采用开放、随机、两周期交叉设计，给药间隔7天，洗脱期至少4周。在给药前以及给药后720分钟内的不同时间点采集用于测定酚妥拉明的血浆样本。血浆浓度通过采用多反应监测（MRM）方法的正离子电喷雾电离的反相液相色谱-串联质谱（LC-MS-MS）进行定量。使用校准曲线和血浆质量控制样本评估该方法的精密度。在整个研究过程中对受试者进行监测。在给药前以及直至720分钟的不同时间点测量收缩压、舒张压和脉搏率。两种产品的耐受性良好。未报告严重不良反应。计算得到的两种化合物的药代动力学参数包括：AUC(0 - 720分钟)、AUC(0 - 无穷大)、C(max)、Ca和k(e)。

结果

比较了达到的最大浓度（C(max)）。Regitine 40毫克制剂的C(max)几何平均比值为Vasomax 40毫克制剂的108.29%（90%置信区间 = 98.58 - 118.96）。比较了曲线下面积（AUC(0 - 720分钟)）。Regitine 40毫克制剂（AUC(0 - 720分钟)）的几何平均比值为Vasomax 40毫克制剂的102.33%（90%置信区间 = 97.21 - 107.72）。