Summary
Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6, whereas in late pregnancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.
Similar content being viewed by others
References
Aitio A (1974) UDP glucuronyltransferase of human placenta. Biochem Pharmacol 23: 2203–2207
Alvan G, Siwers B, Vessman J (1977) Pharmacokinetics of oxazepam in healthy volunteers. Acta Pharmacol Toxicol 40: Suppl. I, 40–46
Bertagni P, Marcucci F, Mussini E, Garattini S (1972) Biliary excretion of conjugated hydroxyl benxodiazepines after administration of several benzodiazepines to rats, guinea pigs, and mice. J Pharm Sci 61: 965–966
Berte F, Manzo L, De Bernardi M, Benzi G (1969) Ability of the placenta to metabolize oxazepam and aminopyrine before and after drug stimulation. Arch Int Pharmacodyn 182: 182–185
Dilts PV, Brinkman CR, Kirschbaum TH, Assali NS (1969) Uterine and systemic hemodynamic interrelationships and their response to hypoxia. Am J Obstet Gynecol 103: 138–143
Dutton GJ (1959) Glucuronide synthesis in foetal liver and other tissues. Biochemistry 71: 141–148
Erkkola R, Kangas L, Pekkarinen A (1973) The transfer of diazepam across the placenta during labour. Acta Obstet Gynecol Scand 52: 167–170
Erkkola R, Kanto J, Sellman R (1974) Diazepam in early human pregnancy. Acta Obstet Gynecol Scand 53: 135–138
Erkkola R, Kanto J, Kangas L, Piiroinen O (1976) Feto-maternal concentrations of diazepam and N-demethyldiazepam after intra-amniotic diazepam injection. Int J Gynecol Obstet 14: 213–216
Garattini S, Mussini E, Marcucci F, Guaitani A (1973) Metabolic studies on benzodiazepines in various animal species. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven Press, New York, pp 75–97
Hirvonen T (1966) Fetal and postnatal development of glucuronide formation in mammalian tissue slices. Ann. Univ. Turku Sarja-Series A. 2. 38
Hytten FE, Leitch I (1971) Physiology of Human Pregnancy, 2nd ed. Blackwell, Oxford, pp 72–107
Juchau MR, Niwander KR, Yaffe SJ (1968) Drug metabolizing systems in homogenates in human immature placentas. Am J Obstet Gynecol 100: 348–356
Kangas L, Kanto J, Erkkola R (1977) Transfer of nitrazepam across the human placenta. Eur J Clin Pharmacol 12: 355–357
Kanto J, Erkkola R, Sellman R (1973) Accumulation of diazepam and N-demethyldiazepam in the fetal blood during labour. Ann Clin Res 5: 375–379
Kanto J, Erkkola R (1974) The feto-maternal distribution of diazepam in early human pregnancy. Ann Chir Gynaecol Fenn 63: 489–491
Kanto J, Erkkola R, Sellman R (1974a) Distribution and metabolism of diazepam in early and late human pregnancy. Postnatal metabolism of diazepam. Acta Pharmacol Toxicol 35: Suppl 36
Kanto J, Erkkola R, Sellman R (1974b) Perinatal metabolism of diazepam. Br Med J 1: 641–642
Mirkin BL (1974) Maternal and fetal distribution of drugs in pregnancy. Clin Pharmacol Ther 14: 643–647
Pelkonen O, Arvela P, Kärki NT (1971) 3,4-benzpyrene and N-methyl-aniline metabolizing enzymes in immature human foetus and placenta. Acta Pharmacol Toxicol 30: 385–391
Pelkonen O (1973) Studies on drug metabolizing enzymes in the human foetus. Dissertation, Oulu
Schwartz MA, Koechlin BA, Postma E, Palmer S, Krol G (1965) Metabolism of diazepam in rat, dog, and man. J Pharmacol Exp Ther 149: 423–435
Sentker HJ (1972) Methodische Untersuchungen zum gaschromatographischen Nachweis von Oxazepam aus Blut und Harn nach Gabe therapeutischer Dosen. Voraussetzung für pharmakokinetische Experimente. Dissertation, Tübingen
Shull HJ, Wilkinson GR, Johnson R, Schenker S (1976) Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Int Med 84: 420–425
de Silva JAE, Schwartz MA, Stefanovic V, Kaplan J, D'Arconte L (1964) Determination of diazepam (Valium) in blood by gas liquid chromatography. Anal Chem 36: 2099–2105
Tomson G, Lunell N-O, Sundwall A, Rane A (1979) Placental passage of oxazepam and its metabolism in mother and newborn. J Pharmacol Exp Ther 25: 74–81
Wynn RM (1968) Morphology of the placenta. In: Assali NS (ed) Biology of gestation. Academic Press, New York and London, pp 153–178
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kangas, L., Erkkola, R., Kanto, J. et al. Transfer of free and conjugated oxazepam across the human placenta. Eur J Clin Pharmacol 17, 301–304 (1980). https://doi.org/10.1007/BF00625804
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00625804