O'Hare M F, Leahey W, Murnaghan G A, McDevitt D G
Eur J Clin Pharmacol. 1983;24(4):521-4. doi: 10.1007/BF00609896.
Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32-36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4 +/- 0.3 ml/min/kg) than in the post-natal phase (1.5 +/- 0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6 +/- 0.6 h ante-natally and 9.3 +/- 0.7 h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10 h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
索他洛尔是一种β-肾上腺素能受体阻滞剂，对6名健康的孕龄在32至36周的孕妇志愿者以及产后至少6周的志愿者进行了用药研究。在这两种情况下，每位志愿者均随机接受静脉注射100毫克索他洛尔和口服400毫克索他洛尔，两次给药之间至少间隔1周的洗脱期。使用荧光法分析血浆样本中的索他洛尔，并研究其药代动力学特征。索他洛尔的全身清除率在产前阶段（2.4±0.3毫升/分钟/千克）显著高于产后阶段（1.5±0.1毫升/分钟/千克）。两个阶段的表观分布容积相似：静脉给药后，消除半衰期产前为6.6±0.6小时，产后为9.3±0.7小时，但消除更快的趋势并不显著。口服给药后的消除半衰期（约10小时）和生物利用度（约90%）并未因怀孕而发生显著改变。有人认为，孕期索他洛尔清除更快可能是由于肾血浆流量和肾小球滤过率增加所致。
