抑酸药对马来酸多潘立酮在健康人体相对生物利用度的影响

Effect of relative bioavailability of domperidone maleate combined with antacids in healthy volunteers

目的观察抑酸药(法莫替丁、鼠李铋镁)对马来酸多潘立酮(健胃药)在健康人体药代动力学的影响。方法10名健康受试者未服和服用抑酸药后,单剂量口服马来酸多潘立酮10mg,用LC/MS/MS测定血药浓度,用Win-NonLin5.0软件计算药代动力学参数,并用Spss12.0软件比较主要药代动力学参数。结果未服和服用抑酸药后,单剂量口服马来酸多潘立酮,其药代动力学参数如下:tmax分别为(0.85±0.24)、(2.20±1.78)h,Cmax分别为(9.68±5.37)、(7.18±4.12)μg.L-1,AUC0～tn分别为(38.18±19.76)、(49.96±10.35)μg.h.L-1。显示服用抑酸药后,马来酸多潘立酮的tmax延长,有显著性差异(P=0.04);AUC0-tn增加,峰浓度降低,但无显著性差异(分别为P=0.1、0.06)。结论在健康人体内,法莫替丁、鼠李铋镁不影响马来酸多潘立酮的吸收程度;但使其吸收速度减慢。

Objective To study the effect of antacids （famotidine and Cascara, bismuth subnitrate and magnesium carbonate） on the pharmacokinetics of domperidone maleate in healthy volunteers. Methods A single oral dose of domperidone maleate 10 mg was given to 10 healthy volunteers under the condition of untaking or taking antacids. Plasma domperidone concentration was determined by a validated LC/MS/MS method. Pharmacokinetic parameters were calculated by WinNonLin 5.0 software and compared the parameters by Spss 12.0 software. Results Under untaking and taking antacids conditions, the main pharmacokinetic parameters were as follows ： tmax were （0. 85 ± 0.24 ） and （2.20 ± 1.78 ） h, Cmax were （9. 68 ±5. 37） and （7. 18 ±4. 12） μg· L^-1, AUCo-tn were （38.18±19.76） and （49.96±10.35） μg· h· L^-1. The absorption of domperidone maleate was delayed significantly, the peak concentration were reduced and area under curve were increased insignificantly when antacids was taken. Conclusion Antacids had significant effects on the absorption rate and had insignificant effects on the absorption extent of domperidone maleate after a single oral dose in healthy volunteer.