Summary
Six women from 14 to 17 weeks pregnant, and 12 woman from 36 to 40 weeks pregnant, were given nitrazepam 5 mg orally about 12 h before legal abortion by hysterotomy in the former group and elective caesarean section in the latter group. The concentration of nitrazepam was determined by gas-liquid chromatography. Binding to plasma proteins was evaluated by separation of the protein-free fraction by ultracentrifugation. In the first group (early pregnancy) the level of nitrazepam was found to be lower in the fetal than in the maternal circulation. The concentration in amniotic fluid was still lower. In the latter group (late pregnancy) the concentration both of unbound and total nitrazepam in maternal and fetal plasma were in equilibrium, which indicated an increase in transplacental transfer in late pregnancy. The percentage of unbound nitrazepam in both cases was 12%.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kangas, L.: Comparison of two gas-liquid chromatographic methods for plasma nitrazepam determination. J. Chromatogr.136, 259–270 (1977)
Kangas, L., Kanto, J., Forsström, J., Iisalo, E.: The protein binding of diazepam and N-demethyl diazepam in patients with poor renal function. Clin. Nephrol.5, 114–118 (1976)
Kangas, L., Kanto, J., Siirtola, T., Pekkarinen, A.: Cerebrospinal-fluid concentrations of nitrazepam in man. Acta pharmacol. toxicol.41, 74–79 (1977)
Kanto, J., Erkkola, R.: The feto-maternal distribution of diazepam in early human pregnancy. Ann. Chir. Gynaec. Fenn.63, 489–491 (1974)
Kanto, J., Erkkola, R., Sellman, R.: Accumulation of diazepam and N-demethyldiazepam in the fetal blood during the labour. Ann. clin. Res.5, 375–379 (1973)
Kanto, J., Kangas, L., Siirtola, T.: Cerebrospinal-fluid concentrations of diazepam and its metabolites in man. Acta pharmacol. toxicol.36, 328–334 (1975)
Krasner, J., Giacoia, G.P., Yaffe, S.J.: Drug protein binding in the newborn infant. Ann. N. Y. Acad. Sci.226, 101–114 (1973)
Mirkin, B.L.: Maternal and fetal distribution of drugs in pregnancy. Clin. Pharmacol. Ther.14, 643–647 (1974)
Müller, W.E., Wollert, U.: Benzodiazepines; specific competitors for the binding of L-tryptophane to human serum albumin. Naynun-Schmiedeberg's Arch. Pharmacol.288, 17–27 (1975)
Rieder, J., Wendt, G.: Pharmacokinetics and metabolism of hypnotic nitrazepam. In: The Benzodiazepines (eds. S. Garattini, E. Mussini and L. O. Randall), pp 99–127. New York: Raven Press 1973
Thiessen, J.J., Sellers, E.M., Denbeigh, P., Dolman, L.: Plasma protein binding of diazepam and tolbutamide in chronic alcoholics. J. clin. Pharmacol.16, 345–351 (1976)
Wynn, R.M.: Morphology of the placenta. In: Biology of gestation I (ed. N.S. Assali) pp 93–184. New York and London: Academic Press 1968
Zingales, I.A.: Detection of chlorpromazine and thioridazine metabolites in human erythrocytes. J. Chromatogr.44, 547–562 (1969)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kangas, L., Kanto, J. & Erkkola, R. Transfer of nitrazepam across the human placenta. Eur J Clin Pharmacol 12, 355–357 (1977). https://doi.org/10.1007/BF00562451
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00562451