Summary
The placental transfer of etozolin and its pharmacologically active metabolite ozolinone was studied in 48 patients during the first (44 patients) and second (4 patients) trimester. 24 patients received a single oral dose of etozolin 400 mg 2–20 h prior to interruption of pregnancy by curettage or prostaglandin infusion. 24 other patients received 3 oral doses of etozolin 400 mg (11 patients) or 800 mg (13 patients) on 3 consecutive days, and pregnancy was terminated 2–10 h after the last dose. The fetal tissue/maternal serum and placental tissue/maternal serum ratios of etozolin and ozolinone were found to lie between 0.3 and 0.6. The serum levels were lower in pregnant than in non-pregnant patients. The low placental and fetal concentrations of etozolin and ozolinone suggest that these drugs may prove useful when a diuretic is indicated in the treatment of oedema and hypertension during pregnancy.
Similar content being viewed by others
References
Beermann B, Groschinsky-Grind M, Fahraeus L, Lindström B (1978) Placental transfer of furosemide. Clin Pharmacol Ther 24: 560–562
Berkowitz RL (1980) Anti-hypertensive drugs in the pregnant patient. Obstet Gynecol Surv 35: 191–204
Biamino G, Kopp H, Rudroff W, Schneider B (1979) Etozolin (Elkapin) in der Behandlung der Herzinsuffizienz. Med Klin 74: 624–630
Franklin ER, Chausseaud LF, Taylor T (1977) The distribution of radioactivity in pregnant rats after repeated oral doses of the diuretic agent etozolin. Arzneim Forsch (Drug Res) 27: 1800–1803
Gladigau V, Vollmer KO (1977) Beschreibung des pharmakokinetischen Verhaltens von Etozolin und dessen Hauptmetaboliten. Arzneim Forsch (Drug Res) 27: 1786–1799
Goossens N, Marshall M (1981) Beeinflussung des Blutgerinnungs-und Fibrinolysesystems und klinischer Parameter durch Etozolin. Med Welt 32: 47–53
Hengy H, Vollmer KO, Gladigau V, Kölle EU (1980) Assay of etozolin and its main metabolite, ozolinone, in plasma by high performance liquid chromatography. Arzneim Forsch (Drug Res) 30: 1788–1790
Herrmann M, Wiegleb J, Leuschner F (1977) Toxikologische Untersuchungen mit Etozolin. Arzneim Forsch (Drug Res) 27: 1758–1767
Kelly JV (1977) Drugs used in the management of toxemia of pregnancy. Clin Obstet Gynecol 20: 395–410
Knauf H, Hasenfuss G, Wais U, Schollmeyer P, Mutschler E (1980) Independence of etozolin elimination of kidney function. Arzneim Forsch (Drug Res) 30: 1791–1793
Ivan E, Liddiard C, Nau H (1980) Placental transfer of etozolin and ozolinone after single and repeated doses. World Conference on Clinical Pharmacology and Therapeutics, London, poster abstract 614
Levy G, Procknal JA, Garettson LK (1975) Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clin Pharmacol Ther 18: 210–214
Liddiard C, Nau H (1981) Determination of etozolin and ozolinone in human plasma and tissues by reversed-phase high-performance liquid chromatography. J Chromatogr 225: 504–508
Merzweiler GA, Gladigau V (1978) Wirkungsvergleich zweier Diuretika — Etozolin und Furosemid — bei gesunden Probanden. Therapiewoche 28: 1–15
Mirkin BL, Singh S (1976) Placental transfer of pharmacologically active molecules. In: Mirkin BL (ed) Perinatal pharmacology and therapeutics. Academic Press, New York, pp 1–69
Mulley BA, Parr GD, Pau WK, Rye RM, Mould JJ, Siddle NC (1978) Placental transfer of chlorthalidone and its elimination in maternal milk. Eur J Clin Pharmacol 13: 129–131
Nation RL (1980) Drug kinetics in childbirth. Clin Pharmacokinet 5: 340–364
Nau H, Liddiard C, Bass R, Lange J, Haase V (1978) Der diaplazentare Übergang sowie der fetale Metabolismus von Pharmaka in der ersten Hälfte der menschlichen Schwangerschaft. In: Schnieders B, Stille G, Grosdanoff P (eds) Embryotoxikologische Probleme in der Arzneimittelforschung. Dietrich Reimer, Berlin, pp 89–96
Nau H, Liddiard C (1978) Placental transfer of drugs during early human pregnancy. In: Neubert D, Merker HJ, Nau H, Langman J (eds) Role of pharmacokinetics in prenatal and perinatal toxicology. Georg Thieme, Stuttgart, Publishing Science Group, Littleton, MA, pp 465–481
Nau H, Rating D, Häuser I, Jäger E, Koch S, Helge H (1980) Placental transfer and pharmacokinetics of primidone and metabolites in neonates and infants of epileptic mothers. Eur J Clin Pharmacol 18: 31–42
Nöschel H, Bonnow A, Möller R, Estel Ch, Müller B (1972) Plazentapassage von Natriumsalizylat. Zentralbl Gynaekol 94: 437–442
Pecorari D, Ragni N, Autera C (1969) Effetti sul neonato della somministrazione die furosemide alla modre durante il travaglio di parto. Acta Biol-Med 40: 3–11
Reynolds F (1979) Transfer of drugs. In: Chamberlain G, Wilkinson A (eds) Placental transfer. Pitman Medical, London, pp 166–181
Riva E, Farina P, Tognoni G, Bottino S, Orrico C, Pardi G (1978) Pharmacokinetics of furosemide in gestosis of pregnancy. Eur J Clin Pharmacol 14: 361–366
Satzinger G (1977) Struktur-Aktivitäts-Betrachtungen zu Etozolin, einem neuartigen Diuretikum. Arzneim Forsch (Drug Res) 27: 1742–1754
Satzinger G (1979) Neuere Entwicklungen in der Chemie der Diuretika. Dtsch Apoth Ztg 44: 1773–1781
Satzinger G, Herrmann M, Vollmer KO, Merzweiler A (1978) Etozolin: A novel diuretic. In: Cragos EJ (ed) Diuretic agents, ACS Symposium Series 83, Am Chem Soc, Washington DC
Vollmer KO, Hodenberg AV, Poisson A, Gladigau V, Hengy H (1977) Resorption, Verteilung, Metabolismus und Ausscheidung von 14C-Etozolin bei Ratte, Hund und Mensch. Arzneim Forsch (Drug Res) 27: 1767–1776
Witter FR, King TM, Blake DA (1981) Adverse effects of cardiovascular drug therapy on the fetus and neonate. Obstet Gynecol 58: 100S-105S
Wladimiroff JW (1975) Effect of furosemide on fetal urine production. Br J Obstet Gynaecol 82: 221–224
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nau, H., Steldinger, R. & Ivan, E. Placental transfer of etozolin and ozolinone during the first half of gestation in man. Eur J Clin Pharmacol 23, 253–260 (1982). https://doi.org/10.1007/BF00547564
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00547564