吗丁啉片剂和混悬剂的生物利用度研究

BIOAVAILABILITY OF DOMPERIDONE TABLET AND SUSPENSION IN NORMAL SUBJECTS

18例健康男性志愿者随机分为两组,分别交叉口服比利时和西安杨森制药公司生产的片剂(t1,t2)和混悬剂(s1,s2),用放射免疫法测定血尿标本,进行相对生物度研究的结果显示,口服两家公司片剂和混悬剂均能很快吸收。口服吗丁啉片t1和t2达峰时间(Tmax)分别为(1.01±0.37和0.74±0.47h;峰浓度(Cmax)分别为13.05±4.46和16.03±5.24μg/l;口服两种片剂均有吸收迟滞时间(tlag),分别为0.16±0.04和0.16±0.06h;二者的药时曲线下面积(AUC)分别为67.38士17.44和70.12士20.07μg·h/l;消除半衰期(t1/2β)分别为8.50±2.18和8.05±3.13h;经t检验,两个产品的上述主要参数均无显著性差异(p>0.05),t1对t2的平均相对生物利用度为106.64±27.47%。口服吗丁啉混悬剂S1和S2,吸收迅速,tmax分别为0.56±0.26和0.65±0.28h、Cmax分别为13.40±4.98和12.90±5.07μg/l;tlag分别为0.08±0.01和0.07±0.01h、AUC分别为75.26±34.96和66.55±32.38μg·h/l;t1/2β分别为7.83±1.57和8.38±1.53h。经t检验,二者的上述主要参数亦均无显著性差异(p>0.05)。S2对S1的相对生物利用度为90.83±20.98%。尿回收率为0.5%。对口服t1的一组受试者尿药量测定结果显示,24h尿中回收原型吗丁啉占给药剂量的0.46±0.14%。

The relative bioavailabibility of domperidone of tablet (s2) and suspension (s2)produced by Xi'an Janssen pharmaceutica and by Belgium Janssen Pharmacutica (t1 and s1) wasstudied in eighteen male subjects. All the subjects fasted overnight, a 10mg dose was taken with 100mlwater, Domperidone concentration was determined by radioimmunoassay, Peak plasma levels of t1and t2 reached 1.01±0.37 and 0.74±0.47h respetively after administration with a lagtime (0.16h) of, The peak levels were 13.05±4.46 and 16.03±5.24μg/l, respectively. Elemination half-lives (t1/2β)s were 8.50±2.18 ! and 8.05±3.13h, respectively. The main pharmacokinetic param-eters of t2 were not significantly different from that of t1, about 0.5% of the dose was excrpted un-changed in the urine, Relative bioavailability of t2 to t1 was 106.64±27.47%, Plasma levels of s1and s2 reached this peaks of 13.40±4.98 and 12.90±5.07 μg/l at 0.56±0.26 and 0.65±0.28 hwith a lagtime (about 0.1h), respectively, The t1/2β s were 7.93±1.57 and 8.38±1.53 h, respec-tively, The main pharmacokinetic parameters of s1 were not significantly different from that of s2,Relative bioavailalibity of s2 to s1 was 90.83 (±20.98) %. With the exreption of the lagtimepharmacokinetic parameters of t1 and s1 were not significantly different from those of T2 and s2.