Moreland T A, McMurdo M E, McEwen J
Drug Development (Scotland) Limited, Ninewells Hospital, Dundee.
Biopharm Drug Dispos. 1989 May-Jun;10(3):311-9. doi: 10.1002/bdd.2510100309.
Twelve healthy male volunteers were studied in a balanced crossover comparison of an intact 240 mg verapamil sustained-release tablet (Securon SR, Isoptin Forte Retard) given once daily for 7 days, and the same dose given as two half tablets. One subject was withdrawn because of asymptomatic second degree heart block on day 3 of verapamil treatment. The mean Cmax after dosing with whole tablets, 143 (95 per cent confidence limits 91.6-223) ng ml-1 was lower than after dosing with half tablets, 160 (107-241) ng ml-1, but this was not significant (p = 0.49). The mean steady-state Cmin values after whole and half tablets were also similar: 22.2 (12.6-39.4) ng ml-1 and 22.0 (16.2-29.9) ng ml-1, respectively (p = 0.96). The mean (+/- S.D.) tmax, AUC0-24 and t 1/2 were not significantly different: whole tablet 3.5 +/- 1.2 h, 1733 +/- 1125 ng.h ml-1 and 10.5 +/- 3.4 h, respectively, and half tablets 3.6 +/- 1.0 h, 1780 +/- 1057 ng.h ml-1 and 9.6 +/- 2.3 h, respectively. The findings for plasma norverapamil were generally similar to those for the parent drug. This investigation indicates that the formulation is sufficiently robust to retain its sustained-release properties when the tablet is halved.
对12名健康男性志愿者进行了一项平衡交叉比较研究，比较每日服用一次完整的240毫克维拉帕米缓释片（Securon SR，异搏定长效片），持续7天，以及服用相同剂量的半片药物的情况。一名受试者在维拉帕米治疗第3天因无症状二度心脏传导阻滞退出研究。服用整片药物后的平均Cmax为143（95%置信区间91.6 - 223）纳克/毫升，低于服用半片药物后的160（107 - 241）纳克/毫升，但差异无统计学意义（p = 0.49）。服用整片和半片药物后的平均稳态Cmin值也相似，分别为22.2（12.6 - 39.4）纳克/毫升和22.0（16.2 - 29.9）纳克/毫升（p = 0.96）。平均（±标准差）tmax、AUC0 - 24和t 1/2差异无统计学意义：整片药物分别为3.5 ± 1.2小时、1733 ± 1125纳克·小时/毫升和10.5 ± 3.4小时，半片药物分别为3.6 ± 1.0小时、1780 ± 1057纳克·小时/毫升和9.6 ± 2.3小时。血浆去甲维拉帕米的研究结果与母体药物的结果总体相似。该研究表明，当片剂减半时，该制剂具有足够的稳定性以保持其缓释特性。
