Drummer O H, Workman B S, Miach P J, Jarrott B, Louis W J
Eur J Clin Pharmacol. 1987;32(3):267-71. doi: 10.1007/BF00607574.
We have measured the plasma concentrations of captopril and total disulfide conjugates of captopril after a 50 mg oral dose in 6 uraemic patients on maintenance dialysis and in 8 hypertensive subjects with normal renal function. The mean peak plasma concentration of captopril was 2.5 times higher (0.447 micrograms X ml-1 vs 0.181 micrograms X ml-1) and the concentrations of the disulfides 4 times higher (3.62 micrograms X ml-1 vs 0.924 micrograms X ml-1) in the uraemic patients. Moreover captopril disulfide conjugates in the uraemic subjects reached peak concentrations at 8 h after the dose and subsequently felt. The apparent plasma half-time was 46 +/- 19 h. Only 15% of these conjugates were removed by dialysis. This marked accumulation of captopril conjugates was associated with a sustained fall in both systolic and diastolic blood pressures. In uraemic patients the mean maximum reduction in systolic and diastolic blood pressures were 37 +/- 7 mmHg and 24 +/- 9 mmHg respectively, occurring 6 h after the dose, compared with 8 +/- 7 and 8 +/- 1 mmHg respectively at 30 min in normal renal function patients. These results are consistent with the results of animal experiments, which show that captopril disulfides can be converted back to free captopril and can contribute to the antihypertensive effect of the drug. They provide a reationale for reducing the dose and frequency of administration of captopril in patients with significant renal impairment.
我们测定了6例维持性透析的尿毒症患者和8例肾功能正常的高血压患者口服50毫克卡托普利后的血浆卡托普利浓度以及卡托普利的总二硫化物结合物浓度。尿毒症患者中卡托普利的平均血浆峰值浓度高出2.5倍（0.447微克/毫升对0.181微克/毫升），二硫化物浓度高出4倍（3.62微克/毫升对0.924微克/毫升）。此外，尿毒症患者体内的卡托普利二硫化物结合物在给药后8小时达到峰值浓度，随后下降。表观血浆半衰期为46±19小时。这些结合物中只有15%可通过透析清除。卡托普利结合物的这种显著蓄积与收缩压和舒张压的持续下降有关。在尿毒症患者中，收缩压和舒张压的平均最大降幅分别为37±7毫米汞柱和24±9毫米汞柱，在给药后6小时出现，而肾功能正常患者在30分钟时分别为8±7毫米汞柱和8±1毫米汞柱。这些结果与动物实验结果一致，动物实验表明卡托普利二硫化物可转化回游离卡托普利，并有助于该药物的降压作用。它们为在严重肾功能损害患者中降低卡托普利剂量和给药频率提供了理论依据。
