本文报道9名健康志愿者口服40mg消旋普萘洛尔后,对映体S(-)和R(+)普萘尔的药代动力学。血浆对映体浓度采用柱前衍生化高效液相色谱法测定。结果显示,S(-)-普萘洛尔的血药浓度较R(+)-普萘洛尔明显偏高,导致较高的血浆峰浓度Cmax(S(-):25....本文报道9名健康志愿者口服40mg消旋普萘洛尔后,对映体S(-)和R(+)普萘尔的药代动力学。血浆对映体浓度采用柱前衍生化高效液相色谱法测定。结果显示,S(-)-普萘洛尔的血药浓度较R(+)-普萘洛尔明显偏高,导致较高的血浆峰浓度Cmax(S(-):25.7±10.1 vs R(+):17.2±7.7μg/l,p<0.01)和较大的药时曲线下面积AUC(S(-):169±56 vs R(+):128±62μg·h/l,p<0.05)。S(-)-普萘洛尔的口服清除率CLoral较R(+)-普萘洛尔明显偏小(S(-):129±59 vs R(+):191±89 l/h,p<0.05),两种对映体的消除半衰期T_(1/2)β没有显著性差异(S(-):5.53±1.56 vs R(+):5.44±2.92h,p>0.05)。对映体药代动力学参数与消旋体配对比较时发现,体内处置过程的立体选择性差异不能完全解释普萘洛尔较大的个体差异和种族差异。展开更多
The pharmacokinetic-pharmacodynamics of propranolol (PPL) and its activemetabolite 4-hydroxypropranolol (4-OH-P) was studied on Chinese subJects by single or multipleoral administration. The efficiency of beta-blockad...The pharmacokinetic-pharmacodynamics of propranolol (PPL) and its activemetabolite 4-hydroxypropranolol (4-OH-P) was studied on Chinese subJects by single or multipleoral administration. The efficiency of beta-blockade was measured as the reduction of heart rates orblood pressure in the supine and upnght positions during rest or exercise period. After a single doseof 40 mg PPL, the plasma concentration of 4-OH-P was quite high, C (m) max and AUC (m) were26. 1±13.2 ng/ml and 180±69 ng.h/ml respectively, which were 50% and 73% of those of PPL.Whileafter multiple dose administration, the plasma PPL concentration increased much greater than that insingle administration and the 4-OH-P/PPL plasma level ratio fell from 0.79±0.64 at single dose toonly 0.48±0.32 at steady-state. The pharmacodynamic half-life of PPL on inbibiting exercising heart-rate was much longer than the halflife of drug concentration (8.78±2.27 vs 4.23±1.33 h. P<0.0 1).The Css 50. plasma concentration at steady-state producing 50% maximal efficacy, was 44.66±35.24ng/ml. The study showed that 4-OH-P is an important active metabolite of PPL and one of thepossible factors causing the considering variations in the response to PPL in Chinese people.展开更多
文摘本文报道9名健康志愿者口服40mg消旋普萘洛尔后,对映体S(-)和R(+)普萘尔的药代动力学。血浆对映体浓度采用柱前衍生化高效液相色谱法测定。结果显示,S(-)-普萘洛尔的血药浓度较R(+)-普萘洛尔明显偏高,导致较高的血浆峰浓度Cmax(S(-):25.7±10.1 vs R(+):17.2±7.7μg/l,p<0.01)和较大的药时曲线下面积AUC(S(-):169±56 vs R(+):128±62μg·h/l,p<0.05)。S(-)-普萘洛尔的口服清除率CLoral较R(+)-普萘洛尔明显偏小(S(-):129±59 vs R(+):191±89 l/h,p<0.05),两种对映体的消除半衰期T_(1/2)β没有显著性差异(S(-):5.53±1.56 vs R(+):5.44±2.92h,p>0.05)。对映体药代动力学参数与消旋体配对比较时发现,体内处置过程的立体选择性差异不能完全解释普萘洛尔较大的个体差异和种族差异。
文摘The pharmacokinetic-pharmacodynamics of propranolol (PPL) and its activemetabolite 4-hydroxypropranolol (4-OH-P) was studied on Chinese subJects by single or multipleoral administration. The efficiency of beta-blockade was measured as the reduction of heart rates orblood pressure in the supine and upnght positions during rest or exercise period. After a single doseof 40 mg PPL, the plasma concentration of 4-OH-P was quite high, C (m) max and AUC (m) were26. 1±13.2 ng/ml and 180±69 ng.h/ml respectively, which were 50% and 73% of those of PPL.Whileafter multiple dose administration, the plasma PPL concentration increased much greater than that insingle administration and the 4-OH-P/PPL plasma level ratio fell from 0.79±0.64 at single dose toonly 0.48±0.32 at steady-state. The pharmacodynamic half-life of PPL on inbibiting exercising heart-rate was much longer than the halflife of drug concentration (8.78±2.27 vs 4.23±1.33 h. P<0.0 1).The Css 50. plasma concentration at steady-state producing 50% maximal efficacy, was 44.66±35.24ng/ml. The study showed that 4-OH-P is an important active metabolite of PPL and one of thepossible factors causing the considering variations in the response to PPL in Chinese people.
