Increased oral clearance of metoprolol in pregnancy
Tóm tắt
The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
Tài liệu tham khảo
Arfwidsson A, Borg KO, Hoffmann KJ, Skånberg I (1976) Metabolism of metoprolol in the rat in vitro and in vivo. Xenobiotica 11: 691–711
Crawford JS, Hooi HWY (1968) Binding of salicylic acid and sulphanilamide in serum from pregnant patients, cord blood and subjects taking oral contraceptives. Br J Anaesth 40: 825–833
Dam M, Christiansen J, Munck O, Mygind KI (1979) Antiepileptic drugs: Metabolism in pregnancy. Clin Pharmacokinet 4: 53–62
Davison JS, Davison MC, Hay DM (1970) Gastric emptying time in late pregnancy and labour. J Obstet Gynaecol 77: 37–41
Dean M, Stock B, Patterson RJ, Levy G (1980) Serum protein binding of drugs during and after pregnancy in humans. Clin Pharmacol Ther 28: 253–261
Ervik M (1975). Acta Pharmacol Toxicol 36[Suppl 5]: 136–144
Johnsson G, Regårdh C (1976) Clinical Pharmacokinetics of β-Adrenoreceptor Blocking Agents. Clin Pharmacokinet 1: 233–263
Johnsson G, Regårdh C (1975). Acta Pharmacol Toxicol 36[Suppl 5]: 7
Krauer B, Krauer F (1977) Drug kinetics in pregnancy. Clin Pharmacokinet 2: 167–181
Lander CM, Edwards WE, Eadie MJ, Tyrer JH (1977) Plasma anticonvulsant concentrations during pregnancy. Neurology 27: 128–131
Landon MJ, Kirkley M (1979) Metabolism of diphenylhydantoin (phenytoin) during pregnancy. Br J Obstet Gynaecol 86: 125–132
Lunell NO, Persson B, Aragon G, Fredholm BB, Åström H (1979) Circulatory and metabolic effects of acute beta1-blockade in severe pre-eclampsia. Acta Obstet Gynaecol Scand 58: 443–445
Lindberg B, Sandström B (1981) How swedish obstetricians manage hypertension in pregnancy — a questionnaire study. Acta Obstet Gynaecol Scand 60: 327–331
Levy G, Procknal JA, Garettson LK (1975) Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clin Pharmacol Ther 18: 210–214
Nilsson A, Hansson B-G, Hökfelt B (1978) Effect of metoprolol on blood glycerol, free fatty acids, triglycerides and glucose in relation to plasma catecholamines in hypertensive patients at rest and following submaximal work. Eur J Clin Pharmacol 13: 5–8
Philipsson A (1977) Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 136: 370–376
Schou M, Amdisen A, Steenstrup OR (1973) Lithium and pregnancy. II Hazards to women given lithium during pregnancy and delivery. Br Med J 2: 137–138
Wilkinson GR, Shand DG (1975) A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390
Wood M, Wood AJJ (1981) Changes in plasma drug binding and α1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther 29: 522–526