匹伐他汀钙片在健康人体内单、多剂量的药动学

目的研究匹伐他汀钙片在中国健康人体内的单、多剂量药动学。方法 30名健康志愿者随机分为3组,分别单剂量口服匹伐他汀钙片l、2、4 mg进行单剂量药动学研究,2 mg剂量组继续给药7 d,进行多剂量药动学研究。血药浓度用液相色谱-串联质谱(LC-MS/MS)法测定。结果健康受试者单剂量给药匹伐他汀钙片l、2、4 mg后,主要的药动学参数分别为tmax分别为(0.61±0.11)、(0.62±0.21)、(0.62±0.11)h,ρmax分别为(23.79±3.54)、(59.66±43.08)、(91.44±33.26) μg·L-1,AUC0-48 h分别为(59.81±12.34)、(126.8±97.90)、(216.8±34.75)μg·h·L-1,tl/2分别为(12.14±1.51)、(10.43±2.24)、(12.33±0.85)h;多剂量给药达稳态时,主要的药动学参数为tmax(0.83±0.14)h,ρmax(51.45±39.93) μg·L-1,AUCss(131.80±110.7)μg·h·L-1,t1/2(11.74±3.22)h,CL(19.92±10.54)L.h-1,ρav(5.49±4.61) μg·L-1,DF(9.43±1.21)%。结论匹伐他汀在连续多次给药后,体内无蓄积现象,血药浓度4 d已达稳态。在1～4 mg剂量范围内匹伐他汀的ρmax、AUC0-48 h和AUC0-∞均与剂量呈线性关系。

Pharmacokinetics of single and multi-dose pitavastatin calcium tablets in healthy volunteers

AIM To study the pharmacokinetics of pitavastatin calcium tablets with a single and multipledose oral administration in Chinese healthy volunteers.METHODS Thirty healthy volunteers were randomly divided into three groups.The volunteers in three groups were administrated with single dose of pitavastatin calcium tablets 1,2,4 mg,respectively,and those who got dose of 2 mg were administrated once a day till the seventh day.Blood samples were measured by LC-MS/MS.RESULTS The main pharmacokinetic parameters of pitavastatin in volunteers who were administrated with a single dose of 1,2,4 mg were as follows: t max(0.61 ± 0.11),(0.62 ± 0.21),(0.62 ± 0.11) h,ρ max(23.79 ± 3.54),(59.66 ± 43.08),(91.44 ± 33.26) μg·L-1,AUC 0-48 h(59.81 ± 12.34),(126.80 ± 97.90),(216.80 ± 34.75) μg·h·L-1,t 1/2(12.14 ± 1.51),(10.43 ± 2.24),(12.33 ± 0.85) h,respectively.The main pharmacokinetic parameters of pitavastatin after multiple-dose administration were as follows: t max(0.83 ± 0.14) h,ρ max(51.45 ± 39.93) μg·L-1,AUC ss(131.80 ± 110.7) μg·h·L-1,t 1 /2(11.74 ± 3.22) h,CL(19.92 ± 10.54) L.h-1,ρ av(5.493 ± 4.610) μg·L-1,DF(9.43 ± 1.21) %.CONCLUSION After administration of multiple-dose pitavastatin,no accumulation occur in vivo.Plasma concentrations of pitavastatin have been in steady state till fourth day.Increase of pitavastatin dosage is positively calculated with increase of ρ max,AUC 0-∞ and AUC 0-48 h.