Sasaki M, Tateishi T, Ebihara A
Department of Clinical Pharmacology and Therapeutics, Jichi Medical School, Tochigi, Japan.
Clin Pharmacol Ther. 1993 Sep;54(3):278-85. doi: 10.1038/clpt.1993.148.
The effects of age and gender on the pharmacokinetics of verapamil stereoisomers were examined. Eighty milligrams of racemic verapamil was given orally to 12 young and 12 elderly healthy subjects, half of whom were women. The area under the plasma concentration-time curves (AUC) of (S)- and (R)-verapamil were greater in the elderly group than in the young group [(S)-/(R)-verapamil (mean +/- SD), 214.4 +/- 123.0/1582.2 +/- 763.0 and 50.4 +/- 36.5/584.9 +/- 252.4 ng.hr/ml for the elderly and young groups, respectively (p < 0.001/p < 0.001)]. Conversely, the apparent oral clearance values of (S)- and (R)-verapamil were significantly smaller in the elderly group than in the young group [(S)-/(R)-verapamil (mean +/- SD), 4.8 +/- 3.0/0.53 +/- 0.21 and 22.5 +/- 21.3/1.30 +/- 0.67 L/hr/kg for the elderly and young groups, respectively (p < 0.01/p < 0.001)]. The ratio of apparent oral clearance of (S)- to (R)-verapamil was significantly smaller in the elderly group than in the young group. As a consequence, the negative chronotropic and dromotropic effect of verapamil was observed in the elderly group. This study suggests that the effect of age on metabolism was greater for (S)-verapamil than for (R)-verapamil.
研究了年龄和性别对维拉帕米立体异构体药代动力学的影响。将80毫克消旋维拉帕米口服给予12名年轻健康受试者和12名老年健康受试者，其中一半为女性。老年组中（S）-和（R）-维拉帕米的血浆浓度-时间曲线下面积（AUC）大于年轻组[（S）-/（R）-维拉帕米（均值±标准差），老年组和年轻组分别为214.4±123.0/1582.2±763.0和50.4±36.5/584.9±252.4 ng·hr/ml（p<0.001/p<0.001）]。相反，老年组中（S）-和（R）-维拉帕米的表观口服清除率值显著低于年轻组[（S）-/（R）-维拉帕米（均值±标准差），老年组和年轻组分别为4.8±3.0/0.53±0.21和22.5±21.3/1.30±0.67 L/hr/kg（p<0.01/p<0.001）]。老年组中（S）-维拉帕米与（R）-维拉帕米的表观口服清除率之比显著低于年轻组。因此，在老年组中观察到维拉帕米的负性变时性和变传导性作用。本研究表明，年龄对（S）-维拉帕米代谢的影响大于对（R）-维拉帕米的影响。
