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目的研究磷酸二甲啡烷糖浆剂在中国健康志愿者中的单次和连续多次给药药代动力学特征。方法 12名健康志愿者,男女各半。单次口服磷酸二甲啡烷糖浆剂10,20,40 mg,多次口服磷酸二甲啡烷糖浆剂20 mg,每天3次,连续给药4 d。用HPLC-MS/MS法测定血浆中二甲啡烷的药物浓度。结果单次口服磷酸二甲啡烷糖浆剂10,20,40 mg后的主要药代动力学参数:Cmax为(0.94±0.44),(2.19±1.40),(5.30±4.83)μg·L-1,AUClast为(11.06±5.74),(26.41±18.08),(53.78±38.28)μg·L-1·h,AUCinf为(12.14±6.02),(28.46±20.21),(57.26±41.40)μg·L-1·h。多次口服磷酸二甲啡烷糖浆剂20 mg后的主要药代动力学参数:Cmax为(5.57±3.64)μg·L-1,AUClast为(83.07±62.51)μg·L-1·h,AUCinf为(88.54±68.14)μg·L-1·h。结论单次给药10,20,40 mg后,二甲啡烷的体内过程符合一级线性动力学过程;连续多次给药20 mg后,二甲啡烷的蓄积因子接近3,符合线性累加。
Objective To study the pharmacokinetics of single and continuous multiple administrations of dNTPs in Chinese healthy volunteers. Methods Twelve healthy volunteers, half male and half female. A single oral dose of dimethyl phosphate disodium syrup 10,20,40 mg, multiple oral doses of dimethyl phosphate disodium syrup 20 mg three times daily for 4 d. The drug concentration of the dimethylamine in plasma was determined by HPLC-MS / MS. Results The main pharmacokinetic parameters of 10,20 and 40 mg dosing tablets were as follows: C max was (0.94 ± 0.44), (2.19 ± 1.40), (5.30 ± 4.83) μg · L -1 , AUClast was (11.06 ± 5.74), (26.41 ± 18.08), (53.78 ± 38.28) μg · L-1 · h, AUCinf was (12.14 ± 6.02), (28.46 ± 20.21), (57.26 ± 41.40) μg · L -1 · h. The main pharmacokinetic parameters after multiple oral administration of 20 mg dimethyldithiophosphate syrup were Cmax (5.57 ± 3.64) μg · L-1, AUClast (83.07 ± 62.51) μg · L-1 · h, AUCinf (88.54 ± 68.14) μg · L-1 · h. Conclusions After the single administration of 10, 20 and 40 mg, the in vivo process of dimethylamine is consistent with the first-order linear kinetic process. After multiple administrations of 20 mg, the accumulation factor of dimethylamine is close to 3, which is in line with the linear accumulation .