Ogata H, Aoyagi N, Kaniwa N, Koibuchi M, Shibazaki T, Ejima A
Int J Clin Pharmacol Ther Toxicol. 1982 Apr;20(4):166-70.
The healthy male volunteers participating in bioavailability tests of diazepam tablets were classified into two groups, high and low acidity groups, on the basis of the acidity of their gastric fluid. This was estimated by the Gastrotest method. The bioavailability parameters of four tablet preparations of diazepam (5 mg) after single administration were compared statistically between the two groups. Subjects with low acidity showed significantly lower diazepam serum levels than subjects with high acidity at 1 and/or 2 h after administration of tablets B, C, and D, which showed slower rates of dissolution at pH 4.6. Tablet B gave a significantly lower peak concentration than the other tablets in the high acidity group, whereas in the low acidity group tablet A gave a higher level than the other tablets. The peak concentration in the low acidity group correlated well with the dissolution rates represented as 1/T70 (time of 70% dissolution) at pH 4.6, but we could not find a good method for determining the dissolution rates except for T50 values with the rotating flask method at pH 4.6; these values significantly correlated with the peak concentrations of the high acidity group. From our results we conclude that the acidity of the gastric fluid affects the bioavailability of a drug such as diazepam, which has a pH-dependent dissolution rate and an especially slow rate of dissolution at pH 3-7.
参与地西泮片生物利用度测试的健康男性志愿者，根据其胃液酸度被分为高酸度组和低酸度组两类。这是通过胃肠测试法估算得出的。对两种酸度组单次服用后地西泮（5毫克）的四种片剂制剂的生物利用度参数进行了统计学比较。酸度较低的受试者在服用片剂B、C和D后1小时和/或2小时的地西泮血清水平显著低于酸度较高的受试者，片剂B、C和D在pH 4.6时的溶解速率较慢。在高酸度组中，片剂B的峰值浓度显著低于其他片剂，而在低酸度组中，片剂A的水平高于其他片剂。低酸度组的峰值浓度与pH 4.6时以1/T70（70%溶解时间）表示的溶解速率密切相关，但除了pH 4.6时旋转烧瓶法的T50值外，我们找不到确定溶解速率的好方法；这些值与高酸度组的峰值浓度显著相关。根据我们的结果，我们得出结论，胃液酸度会影响地西泮等药物的生物利用度，地西泮具有pH依赖性溶解速率，在pH 3 - 7时溶解速率特别慢。
