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阿替洛尔在孕期及产后的药代动力学与药效学

Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum.

作者信息

Hebert Mary F, Carr Darcy B, Anderson Gail D, Blough David, Green Grace E, Brateng Debra A, Kantor Eric, Benedetti Thomas J, Easterling Thomas R

机构信息

Department of Pharmacy, University of Washington, Seattle, WA 98195-7630, USA.

出版信息

J Clin Pharmacol. 2005 Jan;45(1):25-33. doi: 10.1177/0091270004269704.

Abstract

Preexisting hypertension complicates 5% of all pregnancies. The objective of this study was to evaluate steady-state atenolol pharmacokinetics and pharmacodynamics (n = 17) during the second trimester (2nd T), third trimester (3rd T), and 3 months postpartum. Pregnancy as compared to 3 months postpartum (nonpregnant control) resulted in significant (P < .05) changes, including the following: 42% (2nd T) and 50% (3rd T) increase in creatinine clearance, 38% (2nd T) and 36% (3rd T) increase in atenolol renal clearance, 12% (2nd T) and 11% (3rd T) decrease in atenolol half-life, 20% (2nd T) and 28% (3rd T) increase in cardiac output, 15% (2nd T) and 23% (3rd T) increase in resting heart rate, and 22% (2nd T) and 21% (3rd T) decrease in total peripheral resistance in subjects on steady-state oral atenolol for treatment of hypertension in pregnancy. In conclusion, the renal clearance of atenolol along with creatinine clearance is increased during pregnancy. However, this does not translate into an increase in apparent oral clearance of atenolol, possibly related to the high variability in bioavailability. Atenolol administration did not appear to change the pattern of the increase in cardiac output and the decrease in total peripheral resistance, which normally occurs during pregnancy.

摘要

既往高血压使5%的妊娠情况变得复杂。本研究的目的是评估妊娠中期(孕中期)、妊娠晚期(孕晚期)及产后3个月期间稳态阿替洛尔的药代动力学和药效学(n = 17)。与产后3个月(非妊娠对照)相比,妊娠导致了显著(P <.05)变化,包括以下方面:肌酐清除率增加42%(孕中期)和50%(孕晚期),阿替洛尔肾清除率增加38%(孕中期)和36%(孕晚期),阿替洛尔半衰期降低12%(孕中期)和11%(孕晚期),心输出量增加20%(孕中期)和28%(孕晚期),静息心率增加15%(孕中期)和23%(孕晚期),以及接受稳态口服阿替洛尔治疗妊娠高血压的受试者总外周阻力降低22%(孕中期)和21%(孕晚期)。总之,妊娠期间阿替洛尔的肾清除率与肌酐清除率一同增加。然而,这并未转化为阿替洛尔表观口服清除率的增加,这可能与生物利用度的高度变异性有关。阿替洛尔的给药似乎并未改变通常在妊娠期间出现的心输出量增加和总外周阻力降低的模式。

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