Kirch W, Janisch H D, Heidemann H, Rämsch K, Ohnhaus E E
Dtsch Med Wochenschr. 1983 Nov 18;108(46):1757-61. doi: 10.1055/s-2008-1069821.
Simultaneous administration of cimetidine and nifedipine to six healthy volunteers produced an about 80% rise in maximal plasma levels and the area under the plasma level-time curve of nifedipine compared with results on nifedipine administration alone (P less than 0.05). After treatment for one week with 4 X 10 mg nifedipine daily and 3 X 200 mg cimetidine daily and 400 mg at night plasma level peaks of nifedipine averaged 87.7 +/- 19.1 ng/ml, while after 4 X 10 mg nifedipine alone they were only 46.1 +/- 10.6 ng/ml. Ranitidine produced an approximately 25%, nonsignificant, rise in plasma level-time curve and peak plasma levels of nifedipine. Seven hypertensives (WHO stage I and II) had a mean arterial blood pressure level of 127 +/- 2.5 mm Hg after two-week placebo administration, and of 109 +/- 2.38 mm Hg after four weeks of nifedipine alone at 4 X 10 mg daily (P less than 0.01). After additional administration of 1 g cimetidine daily for two weeks the mean blood pressure fell significantly to 95 +/- 3.1 mm Hg (P = 0.02), while blood pressure fell to 103 +/- 3.88 mm Hg after two weeks of additional administration of 300 mg ranitidine daily, a fall which was not significant (P greater than 0.05). The interaction of nifedipine and cimetidine is thus of clinical significance because of its pharmacodynamic effect.
对6名健康志愿者同时给予西咪替丁和硝苯地平,与单独给予硝苯地平的结果相比,硝苯地平的最大血浆浓度和血浆浓度-时间曲线下面积升高了约80%(P<0.05)。每天服用4次10mg硝苯地平、3次200mg西咪替丁且晚上服用400mg,治疗1周后,硝苯地平的血浆浓度峰值平均为87.7±19.1ng/ml,而单独服用4次10mg硝苯地平时,其血浆浓度峰值仅为46.1±10.6ng/ml。雷尼替丁使硝苯地平的血浆浓度-时间曲线和血浆浓度峰值升高了约25%,但无统计学意义。7名高血压患者(WHO I期和II期)在服用两周安慰剂后平均动脉血压水平为127±2.5mmHg,每天服用4次10mg硝苯地平单独治疗4周后为109±2.38mmHg(P<0.01)。在每天额外服用1g西咪替丁两周后,平均血压显著降至95±3.1mmHg(P=0.02),而在每天额外服用300mg雷尼替丁两周后,血压降至103±3.88mmHg,下降不显著(P>0.05)。因此,硝苯地平和西咪替丁的相互作用因其药效学效应而具有临床意义。