Dyderski Stanisław, Grześkowiak Edmund, Drobnik Leon, Szałek Edyta, Balcerkiewicz Monika, Dubai Vitali
Department of Clinical Pharmacy and Biopharmacy, K. Marcinkowski University of Medical Sciences, Poznań, Poland.
Arzneimittelforschung. 2004;54(5):298-302. doi: 10.1055/s-0031-1296974.
The bioavailability of drotaverine (CAS 14009-24-6) was investigated after oral administration of a drotaverine capsule preparation (20 mg Droxa mite) and compared to that of a reference tablet preparation. The preparations were investigated in 23 healthy volunteers, aged between 20 and 27 years, according to a randomised two-way, cross-over design in the fasted state. Blood samples for determination of drotaverine plasma concentrations were collected at pre-defined time points up to 30 h following drug administration. A washout period of two weeks separated both treatment periods. Drotaverine plasma concentrations were determined by means of a validated HPLC method (UV detector, imipramine HCl salt as an internal standard). The limit of detection was 6 ng/ml. Values of 1593.92 +/- 949.70 ng x h/l (95% confidence interval (CI): 1183.20-2004.60) for the test and 1705.48 +/- 737.78 ng x h/l (95% CI: 1386.40-2024.50) for the reference preparation AUC(0-infinity) demonstrate a nearly identical extent of drug absorption. Maximum concentrations--Cmax of 121.89 +/- 37.03 ng/ml (95% CI: 104.05-139.80) and 121.85 +/- 37.97 ng/ml (95% CI: 107.09-135.74) and time to reach maximum plasma concentration--Tmax of 1.29 +/- 0.42 h (95% CI: 1.11-1.48) and 1.14 +/- 0.34 h (95% CI: 0.99-1.29) achieved for the test and reference preparations did not differ significantly. The relative bioavailability (AUC(0-infinity) ratio test/reference) and Cmax ratio test/reference were 103.15% (90% CI: 81.68-124.60) and 103.74% (90% CI: 94.10-113.38), respectively. AUC was calculated using two different methods. There were no significant differences between the obtained values. Since the 90% CI for both, AUC and Cmax ratios were within the 80-125% interval proposed by the European Agency for the Evalution of Medicinal Products (CPMP) and the Food and Drug Administration, it is concluded that the new drotaverine capsule formulation is therapeutically equivalent to the conventional formulation for both, the extent and the rate of absorption after single dose administration in healthy volunteers.
在口服屈他维林胶囊制剂（20毫克屈他维林）后，对屈他维林（CAS 14009-24-6）的生物利用度进行了研究，并与参比片剂制剂进行了比较。根据随机双向交叉设计，在23名年龄在20至27岁之间的健康志愿者处于空腹状态下对这些制剂进行了研究。在给药后长达30小时的预定义时间点采集血样，用于测定屈他维林血浆浓度。两个治疗周期之间间隔两周的洗脱期。通过经过验证的高效液相色谱法（紫外检测器，盐酸丙咪嗪盐作为内标）测定屈他维林血浆浓度。检测限为6纳克/毫升。试验制剂的AUC(0-无穷大)值为1593.92±949.70纳克·小时/升（95%置信区间(CI)：1183.20-2004.60），参比制剂的该值为1705.48±737.78纳克·小时/升（95%CI：1386.40-2024.50），表明药物吸收程度几乎相同。试验制剂和参比制剂的最大浓度——Cmax分别为121.89±37.03纳克/毫升（95%CI：104.05-139.80）和121.85±37.97纳克/毫升（95%CI：107.09-135.74），以及达到最大血浆浓度的时间——Tmax分别为1.29±0.42小时（95%CI：1.11-1.48）和1.14±0.34小时（95%CI：0.99-1.29），差异均无统计学意义。相对生物利用度（AUC(0-无穷大)试验/参比比值）和Cmax试验/参比比值分别为103.15%（90%CI：81.68-124.60）和103.74%（90%CI：94.10-113.38）。AUC使用两种不同方法计算。所得值之间无显著差异。由于AUC和Cmax比值的90%CI均在欧洲药品评估局（CPMP）和美国食品药品监督管理局提出的80-125%区间内，因此得出结论，新的屈他维林胶囊制剂在健康志愿者单剂量给药后的吸收程度和吸收速率方面与传统制剂在治疗上等效。
