Hendershot P E, Fleishaker J C, Lin K M, Nuccio I D, Poland R E
Clinical Pharmacology II, Pharmacia and Upjohn, Inc, Kalamazoo, MI 49007, USA.
Psychopharmacology (Berl). 2001 May;155(2):148-53. doi: 10.1007/s002130100696.
Ethnicity can affect the pharmacokinetics and pharmacodynamics of psychopharmacologic drugs.
Reboxetine disposition differences among Asians, blacks, and Caucasians were examined.
Healthy subjects (12 Asians, 12 blacks, 12 Caucasians) received a single oral dose of one 4-mg reboxetine tablet in an open label, parallel study design. Plasma concentrations of reboxetine enantiomers [R,R(-) reboxetine and predominantly active S,S(+) reboxetine] were quantified using HPLC-MS-MS. Plasma unbound fractions of reboxetine enantiomers were evaluated by equilibrium dialysis. Ethnic group effects on pharmacokinetic parameters were assessed by ANOVA.
Mean S,S(+) reboxetine CLPO for blacks was significantly greater, compared to Asians and Caucasians (154+/-82 ml/min, 101+/-19 ml/min and 101+/-18 ml/min, respectively). Mean S,S(+) reboxetine free fractions (fu) were significantly greater for Asians and blacks, compared to Caucasians (3.04+/-1.28%, 2.89+/-0.69%, and 1.99+/-0.58%, respectively). S,S(+) Reboxetine unbound clearance (CLu) was significantly less for Asians, compared to blacks and Caucasians (3742+/-1468 ml/min, 5187+/-2027 ml/min, and 5294+/-1163 ml/min, respectively). S,S(+) Reboxetine mean unbound AUC (AUCu) in these groups were 20.2+/-7.1 ng.h/ml, 14.6+/-5.1 ng.h/ml, and 13.2+/-3.2 ng.h/ml, respectively. AUCu was significantly greater for Asians. CLu and AUCu did not differ significantly between blacks and Caucasians. Ethnic effects of R,R(-) reboxetine were similar to those observed for S,S(+) reboxetine.
The AUCu difference between Asian and black and Caucasian subjects was modest. Tolerability differences among groups were not observed. No dosage adjustment is necessary for Asians or blacks.
种族可能会影响精神药物的药代动力学和药效学。
研究亚洲人、黑人和高加索人中瑞波西汀的处置差异。
在一项开放标签、平行研究设计中，健康受试者（12名亚洲人、12名黑人、12名高加索人）口服一剂4毫克的瑞波西汀片。使用高效液相色谱-串联质谱法定量测定瑞波西汀对映体[R,R(-)瑞波西汀和主要具有活性的S,S(+)瑞波西汀]的血浆浓度。通过平衡透析评估瑞波西汀对映体的血浆未结合分数。通过方差分析评估种族对药代动力学参数的影响。
与亚洲人和高加索人相比，黑人的平均S,S(+)瑞波西汀CLPO显著更高（分别为154±82毫升/分钟、101±19毫升/分钟和101±18毫升/分钟）。与高加索人相比，亚洲人和黑人的平均S,S(+)瑞波西汀游离分数（fu）显著更高（分别为3.04±1.28%、2.89±0.69%和1.99±0.58%）。与黑人和高加索人相比，亚洲人的S,S(+)瑞波西汀未结合清除率（CLu）显著更低（分别为3742±1468毫升/分钟、5187±2027毫升/分钟和5294±1163毫升/分钟）。这些组中S,S(+)瑞波西汀的平均未结合AUC（AUCu）分别为20.2±7.1纳克·小时/毫升、14.6±5.1纳克·小时/毫升和13.2±3.2纳克·小时/毫升。亚洲人的AUCu显著更高。黑人和高加索人之间的CLu和AUCu没有显著差异。R,R(-)瑞波西汀的种族效应与S,S(+)瑞波西汀观察到的相似。
亚洲人与黑人和高加索人受试者之间的AUCu差异不大。未观察到组间耐受性差异。亚洲人或黑人无需调整剂量。
