Hing Jeremy P, Piotrovsky Vladimir, Kimko Hui, Brashear H Robert, Zhao Qinying
Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ, USA.
Curr Med Res Opin. 2005 Apr;21(4):483-8. doi: 10.1185/030079905X38213.
To demonstrate using pharmacokinetic (PK) modeling and simulation, that the PK that the PK parameters for drug exposure with galantamine parameters for drug exposure with galantamine immediate-release (IR) tablet and galantamine extended-release (ER) capsule are comparable in patients with Alzheimer's disease (AD) during in patients with Alzheimer's disease (AD) during the switch from twice-daily IR tablet at steady state to the new once-daily ER capsule, and to support a recommendation that patients receiving the IR tablet at steady state can be successfully switched to the ER capsule at the same daily dosage with no titration period.
Simulations were performed using a population PK model developed from clinical studies with IR galantamine in the target AD population, in combination with IR and ER absorption parameters obtained from a PK study in healthy volunteers which showed similar results. PK simulations were performed for the switch from IR tablet 8 mg b.i.d. to ER capsule 16 mg q.d. and from IR tablet 12 mg b.i.d. to ER capsule 24 mg q.d.
This simulation predicted that patients switched from the IR tablet to the ER capsule, the PK parameters for drug exposure on the first day of ER treatment would be similar to those of IR treatment at steady state. After steady state was achieved with ER galantamine, values for peak concentration and trough concentration were slightly lower (5% and 18%, respectively) than those seen at steady state for IR galantamine; this finding is considered to have no clinical implications. Area under the curve (AUC) with ER galantamine was similar to that seen at steady state with IR galantamine.
These results suggest that no titration period is required in patients receiving stable doses of twice-daily IR galantamine who are switched to once-daily ER galantamine. The once-daily dosage regimen of ER galantamine without a titration period should prove convenient for AD patients and their caregivers and should increase treatment compliance.
通过药代动力学（PK）建模与模拟，证明在阿尔茨海默病（AD）患者中，从稳态每日两次服用加兰他敏速释（IR）片转换为每日一次服用加兰他敏缓释（ER）胶囊时，加兰他敏速释片和加兰他敏缓释胶囊的药物暴露PK参数具有可比性，并支持一项建议，即接受稳态IR片治疗的患者可以成功转换为相同日剂量的ER胶囊，无需滴定期。
使用从目标AD人群中关于IR加兰他敏的临床研究开发的群体PK模型进行模拟，并结合从健康志愿者的PK研究中获得的IR和ER吸收参数，这些研究显示了相似的结果。对从8mg bid的IR片转换为16mg qd的ER胶囊以及从12mg bid的IR片转换为24mg qd的ER胶囊进行PK模拟。
该模拟预测，从IR片转换为ER胶囊的患者，ER治疗第一天的药物暴露PK参数将与稳态IR治疗时相似。在加兰他敏ER达到稳态后，峰浓度和谷浓度值略低于加兰他敏IR稳态时的值（分别为5%和18%）；这一发现被认为无临床意义。加兰他敏ER的曲线下面积（AUC）与加兰他敏IR稳态时相似。
这些结果表明，接受稳定剂量每日两次IR加兰他敏治疗并转换为每日一次ER加兰他敏的患者无需滴定期。无需滴定期的加兰他敏ER每日一次给药方案对AD患者及其护理人员应是方便的，并应提高治疗依从性。
