中国临床药学杂志

目的研究环孢素与十一酸睾酮在大鼠体内药动学的相互作用。方法采用22只雄性健康大鼠随机分成4组进行2轮试验。第1轮试验中A、B组(每组5只)大鼠分别灌胃给予环孢素20和40mg·kg-1,C、D组(每组6只)大鼠分别灌胃给予十一酸睾酮10.67和21.34mg·kg-1;第2轮试验中A、C组大鼠合为低剂量组,予环孢素20mg·kg-1+十一酸睾酮10.67mg·kg-1,B、D组大鼠合为高剂量组,予环孢素40mg·kg-1+十一酸睾酮21.34mg·kg-1,均连续给药7d。给药后各时间点大鼠全血中环孢素与血清中睾酮的浓度采用酶联免疫法(ELISA)测定,药-时数据应用DAS 2.0程序拟合,计算药动学参数并进行比较。结果在第1轮和第2轮试验中,A组大鼠全血中环孢素的ρmax分别为(408.30±9.61)和(430.29±7.99)μg·L-1,AUC0→∞分别为(35 230.98±1 256.42)和(40 749.93±1 325.86)μg·h·L-1;B组大鼠全血中环孢素的ρmax分别为(418.97±15.62)和(405.71±15.17)μg·L-1,AUC0→∞分别为(41 887.92±2 751.79)和(47 890.33±3 052.64)μg·h·L-1;C组大鼠血清中睾酮的cmax分别为(22.95±1.07)和(23.81±0.39)nmol·L-1,AUC0→∞分别为(2 146.99±915.65)和(2 308.84±725.47)nmol·h·L-1;D组大鼠血清中睾酮的cmax分别(24.49±0.43)和(25.11±0.43)nmol·L-1,AUC0→∞分别为(2 434.57±985.15)和(2 666.68±1 027.05)nmol·h·L-1。即在同等剂量的单剂量给药或联合给药,大鼠全血中环孢素与血清中睾酮主要药动学参数t1/2、CL/F、AUC等之间差异均没有统计学意义。结论环孢素与十一酸睾酮在大鼠体内药动学相互作用不显著。

AIM To study pharmacokinetic interactions of ciclosporin and testosterone undecanoate in rats.METHODS A total of 22 healthy male rats were randomly divided into 4groups.Groups A and B were ciclosporin groups(n=5for each group),groups C and D was testosterone undecanoate groups(n=6for each group).The main pharmacokinetic parameters of groups with only ciclosporin(20mg·kg-1for group A;40mg·kg-1 for group B)or testosterone undecanoate(10.67mg·kg-1for group C;21.34mg·kg-1for group D)and the combination of the two drugs were compared.Ciclosporin and testosterone undecanoate blood concentrations were measured by enzyme-linked immunosorbent assay(ELISA).The corresponding pharmacokinetic parameters were calculated by DAS 2.0software.RESULTS In the first and the second rounds experiment,in group A the rat plasma ciclosporinρmaxwere(408.30±9.61)and(430.29±7.99)μg·L-1,AUC0→∞of(35 230.98±1 256.42)and(40 749.93±1325.86)μg·h·L-1;in group B the rat plasma ciclosporinρmaxwere(418.97±15.62)and(405.71±15.17)μg·L-1,AUC0→∞were(41 887.92±2 751.79)and(47 890.33±3 052.64)μg·h·L-1;in group C the rat serum testosterone cmax were(22.95±1.07)and(23.81±0.39)nmol·L-1,AUC0→∞were(2 146.99±915.65)and(2 308.84±725.47)nmol·h·L-1;in group D the rat serum testosterone cmax were(24.49±0.43)and(25.11±0.43)nmol·L-1,AUC0→∞ were(2 434.57±985.15)and(2 666.68±1 027.05)nmol·h·L-1.That was,under the same dose of a single dose administration or co-administration plasma ciclosporin and serum testosterone in rat in the main pharmacokinetic parameters,betweent1/2,CL/Fand AUC,etc,the difference was not statistically significant.CONCLUSION Ciclosporin and testosterone undecanoate in vivo pharmacokinetic drug interactions are not significant.