Li Shihong, Xu Mingzhen, Li Huqun, Du Juan, Li Weiyong
Department of Pharmacy, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei University of Chinese Medicine, Wuhan, China.
Adv Ther. 2016 Oct;33(10):1704-1714. doi: 10.1007/s12325-016-0383-9. Epub 2016 Jul 21.
The aim of this study was to evaluate the pharmacokinetics (PK) of single and multiple doses of oral lafutidine tablets and the effect of food on the PK properties in healthy Chinese subjects. The tolerability and the effect of gender on the PK properties were also evaluated to acquire more PK information.
Three PK studies were conducted in 12 healthy Chinese subjects (6 male, 6 female). Study 1 was a single-dose, three-period, three-dose level (10, 20, and 40 mg), three-sequence cross-over study under fasting conditions. Study 2 was a repeat-dose study (10 mg twice daily over 6 days; all 12 subjects). Study 3 was a two-period, two-sequence cross-over single-dose (10 mg) food interaction study. All randomizations (study 1, study 3) were done to ascertain 1:1 gender ratio per sequence. A validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method was used to determine plasma lafutidine concentrations. PK parameters were calculated by the non-compartmental method.
The area under the time-concentration curve (AUC) and maximum plasma concentration (C ) of lafutidine tablets were dose-independent in the single-dose study among these healthy volunteers. The PK parameters of the multiple-dose study were inconsistent with the single study. After administration of a single dose of 10 mg under either fed or fasting conditions, we found that food may not affect the degree of absorption of the lafutidine tablets, but it may slow down the absorption rate. This is shown by the fact that the AUC showed no significant difference while the peak time was significantly delayed under fed conditions.
The PK of lafutidine showed dose proportionality. There was no significant accumulation of lafutidine tablets with multiple dosing. Food did not affect the degree of lafutidine absorption, but it did reduce the rate of absorption. Further study is needed regarding the effect of gender on lafutidine. Lafutidine was well tolerated within the dose range 10-40 mg, and no serious adverse events were observed.
本研究旨在评估单次及多次口服拉呋替丁片在健康中国受试者中的药代动力学（PK），以及食物对其PK特性的影响。同时评估了耐受性及性别对PK特性的影响，以获取更多PK信息。
对12名健康中国受试者（6名男性，6名女性）进行了三项PK研究。研究1为在禁食条件下进行的单剂量、三周期、三剂量水平（10、20和40毫克）、三序列交叉研究。研究2为重复剂量研究（12名受试者，每日两次，每次10毫克，共6天）。研究3为两周期、两序列交叉单剂量（10毫克）食物相互作用研究。所有随机分组（研究1、研究3）均确保每个序列的性别比例为1:1。采用经过验证的液相色谱串联质谱（LC/MS/MS）方法测定血浆拉呋替丁浓度。通过非房室模型方法计算PK参数。
在这些健康志愿者的单剂量研究中，拉呋替丁片的药时曲线下面积（AUC）和最大血浆浓度（C）与剂量无关。多次给药研究的PK参数与单次给药研究不一致。在进食或禁食条件下单次给予10毫克后，我们发现食物可能不会影响拉呋替丁片的吸收程度，但可能会减慢吸收速率。这表现为进食条件下AUC无显著差异，而达峰时间显著延迟。
拉呋替丁的PK呈剂量正比关系。多次给药时拉呋替丁片无明显蓄积。食物不影响拉呋替丁的吸收程度，但会降低吸收速率。关于性别对拉呋替丁的影响还需要进一步研究。拉呋替丁在10 - 40毫克剂量范围内耐受性良好，未观察到严重不良事件。
