Summary
Placental transfer of pinazepam and its metabolite N-desmethyldiazepam was investigated in 25 pregnant women at term. Pinazepam was administered orally as a single (10 mg) dose to 13 women, or in multiple doses of 5 mg daily to 12 women. The dose-delivery interval ranged between 1 and 26 h for the single dose, and the period between the last of the multiple doses and delivery was 1.4 to 24 h. Pinazepam and N-desmethyldiazepam were measured in plasma obtained from the umbilical vein and from the mother, at delivery. Pinazepam was only detectable in plasma after the 10 mg dose. The drug did not reach an apparent equilibrium between fetal and maternal plasma. The average (±SEM) cord/maternal ratio of plasma pinazepam concentrations was 0.64±0.07. N-desmethyldiazepam was detectable on each occasion. Its concentration in the plasma from the cord vein became higher than that in the maternal specimens 1–2 h after administration of the parent drug. Little N-desmethyldiazepam was excreted in breast milk.
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Pacifici GM, Placidi GF, Fornaro P, Gomeni R (1982) Pinazepam: a precursor of N-desmethyldiazepam. Eur J Clin Pharmacol 22: 225–228
Pacifici GM, Cuoci L, Placidi GF (1982) Disposition, distribution and liver first-pass effect of pinazepam in the rat. Drug Metab Disp 10: 180–182
Pacifici GM, Placidi GF (1982) First pass effect of pinazepam in the rabbit liver. Eur J Drug Metab Disp 7: 119–122
Pacifici GM, Placidi GF (1977) Rapid and sensitive electron-capture gas chromatographic method for the determination of pinazepam and its metabolites in human plasma, urine and milk. J Chromatogr 135: 133–139
De Silva JAF, D'Arconte L, Kaplan J (1964) The determination of blood levels and the placental transfer of diazepam in humans. Curr Ther Res 6: 115–119
Cavanagh D, Condo CS (1964) Diazepam — a pilot study of drug concentrations in maternal blood, amniotic fluid and cord blood. Curr Ther Res 6: 122–126
Lean TH, Ratnam SS, Sivasamboo R (1968) Use of benzodiazepines in the management of eclampsia. J Obstet Gynaecol (Br Commonw) 75: 856–862
Stenchever MA, Frankel RB, Jarvis JA, Veress K (1969) Some effects of diazepam in human cells in vitro. Am J Obstet Gynecol 15: 836–842
Scher J, Hailey DM, Beard RW (1972) The effects of diazepam on the fetus. J Obstet Gynaecol (Br Commonw) 79: 635–638
Berger R, Green G, Melnick A (1975) Cardiac arrest caused by oral diazepam intoxication. Clin Pediatr 14: 842–844
Shannon RW, Fraser GP, Aitken RG, Harper JR (1972) Diazepam in preeclamptic toxaemia with special reference to its effect on the new born infant. Br J Clin Pract 26: 271–275
Cree JE, Meyer J, Hailey DM (1973) Diazepam in labour: its metabolism and effect on the clinical condition and thermogenesis of the newborn. Br Med J 4: 251–255
Forfar JO, Nelson MM (1973) Epidemiology of drugs taken by pregnant women: drugs that may effect the fetus adversely. Clin Pharmacol Ther 14: 632–642
Reba MH (1973) Drugs ingested by pregnant women. Clin Pharmacol Ther 14: 654–659
Kanto J, Erkkola R, Sellman R (1973) Accumulation of diazepam and N-desmethyldiazepam in the fetal blood during the labour. Ann Clin Res 5: 375–379
Mandelli M, Morselli PL, Nordio S, Pardi G, Principi N, Sereni F, Tognoni G (1975) Placental transfer of diazepam and its disposition in the newborn. Clin Pharmacol Ther 17: 564–572
Haram K, Bakke OM, Johannessen KH, Lund T (1978) Transplacental passage of diazepam during labour: influence of uterine contraction. Clin Pharmacol Ther 24: 590–599
McAllister CB (1980) Placental transfer and neonatal effects of diazepam when administered to women just before delivery. Br J Anaesth 52: 423–427
Kangas L, Kanto J, Erkkola R (1977) Transfer of nitrazepam across the human placenta. Eur J Clin Pharmacol 12: 355–357
Tomson G, Lunell NO, Sundwall A, Rane A (1979) Placental passage of oxazepam and its metabolism in mother and newborn. Clin Pharmacol Ther 25: 74–81
Kangas L, Erkkola R, Kanto J, Eronen M (1980) Transfer of free and conjugated oxazepam across the human placenta. Eur J Clin Pharmacol 17: 301–304
McBride RJ, Dundee JW, Moore J, Toner W, Howard PJ (1979) A study of the plasma concentrations of lorazepam in mother and neonate. Br J Anaesth 51: 971–978
Rey E, Giraux P, d'Athis PH, Turquais JM, Chavinie J, Olive G (1979) Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate. Eur J Clin Pharmacol 15: 181–185
Erkkola R, Kanto J, Sellman R (1974) Diazepam in early human pregnancy. Acta Obstet Gynecol Scand 53: 135–138
Green TP, O'Dea RF, Mirkin BL (1979) Determinants of drugs disposition and effect on the fetus. Ann Rev Pharmacol Toxicol 19: 285–322
Nau H, Liddiard C, Brendel K, Wittfoht W, Lange J (1977) Benzodiazepines metabolism studies in organ and isolated cell cultures of human fetal liver by a gas-chromatographymass spectrometry and combined techniques in medicine, clinical chemistry and clinical biochemestry; Eggstein M, Liebich HM (eds) Symposium Tübingen, pp 346–358
Pacifici GM, Cuoci L, Placidi GF (1983) Disposition, distribution, plasma protein binding and biliary excretion of pinazepam after i. p. administration to rat. Eur J Drug Metab Disp 8: 209–217
Brandt R (1976) Passage of diazepam and desmethyldiazepam into breast milk. Arzneimittelforsch 26: 454–457
Gurodischer R, Jusko WJ, Summer JY (1975) Tissue and erythrocyte distribution of digoxin in infants. Clin Pharmacol Ther 19: 256–263
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Pacifici, G.M., Cuoci, L., Guarneri, M. et al. Placental transfer of pinazepam and its metabolite N-desmethyldiazepam in women at term. Eur J Clin Pharmacol 27, 307–310 (1984). https://doi.org/10.1007/BF00542165
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DOI: https://doi.org/10.1007/BF00542165