Skip to main content
SpringerLink
Log in

Drug Kinetics in Pregnancy

  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Any drug given to a pregnant woman must be considered as possibly harmful to the fetus, since all drugs administered to the mother cross the placental membrane, although at different rates. Important physiological changes occur in pregnancy, which may influence the kinetics of drugs. Differences in gastrointestinal function are likely to alter drug absorption rates in the stomach or gut. Ventilatory alterations modify pulmonary drug absorption or elimination. Important changes in haemodynamics and alterations in body water compartments influence drug distribution and elimination. Renal drug elimination is generally enhanced, whereas hepatic drug elimination may be modified in different ways.

Computerised pharmacokinetic models representing the compartmental aspects of the fetal-maternal unit and fetal-maternal drug interrelationships may be used to predict kinetic consequences of fetal drug exposure. Such information may be a useful guide for the clinical use of drugs during pregnancy, particularly for treatment of fetal disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ackermann, E. and Richter, K.: Diazepam metabolism in human fetal liver microsomes; in Morselli, Garattini and Sereni (Eds) Basic and therapeutic aspects of perinatal pharmacology, p.311–318 (Raven Press, New York 1975).

    Google Scholar 

  • Amon, I. and Amon, K.: Zum Uebertritt von Arzneimitteln in das Fruchtwasser. Zentralblatt fur Gynakologie 98: 961–969 (1976).

    PubMed  CAS  Google Scholar 

  • Asling, J.H. and Way, E.L.: Placental transfer of drugs; in La Du, Mandel and Way (Eds) Fundamentals of drug metabolism and drug disposition, p.88 (Williams and Wilkins, Baltimore 1972).

    Google Scholar 

  • Assali, N.S.; Rauramot, L. and Peltonen, T.: Measurement of uterine blood flow and uterine metabolism. American Journal of Obstetrics and Gynecology 79: 86–98 (1960).

    PubMed  CAS  Google Scholar 

  • Benowitz, N.L. and Meister, W.: Pharmacokinetics in patients with cardiac failure. Clinical Pharmacokinetics 1: 389–405 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Bobok, I.; Czako, G.; Csernyanszky, H. and Ludmany, K.: Lipoids in maternal cord and newborn blood serum. Acta Paediatrica Academiae Scientiarum Hungaricae 15: 95–100 (1974).

    PubMed  CAS  Google Scholar 

  • Chatfield, W.R.; Schramm, B.M. and Richmond, W.J.: The absorption of ampicillin in late pregnancy and labour. New Zealand Medical Journal 80: 500–501 (1974).

    PubMed  CAS  Google Scholar 

  • Chignell, C.F.; Vesell, E.S.; Starkweather, D.K. and Berlin, Ch.M.: The binding of sulfaphenazol to fetal, neonatal and adult human plasma albumin. Clinical Pharmacology and Therapeutics 12: 897–902 (1971).

    PubMed  CAS  Google Scholar 

  • Crawford, J.S. and Hooi, H.W.Y.: Binding of salicylic acid and sulphanilamide in serum from pregnant patients, cord blood and subjects taking oral contraceptives. British Journal of Anesthesiology 40: 825–833 (1968).

    Article  CAS  Google Scholar 

  • Cree, J.E.; Meyer, J. and Hailey, D.M.: Diazepam in labour: Its metabolism and effect on the clinical condition and thermogenesis of the newborn. British Medical Journal 4: 251–255 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Cugell, D.W.; Frank, N.R.; Gaensler, E.A. and Badger, T.L.: Pulmonary function in pregnancy. American Review of Tuberculosis 67: 568–597 (1953).

    PubMed  CAS  Google Scholar 

  • Dancis, J.; Braverman, N. and Lind, J.: Plasma protein synthesis in the human fetus and placenta. Journal of Clinical Investigation 36: 398–404 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Davis, M.; Simmons, G.J.; Dordoni, B.; Maxwell, J.D. and Williams, R.: Induction of hepatic enzymes during normal human pregnancy. The Journal of Obstetrics and Gynaecology of the British Commonwealth 81: 690–694 (1973).

    Article  Google Scholar 

  • Davison, J.M. and Hytten, F.E.: Glomerular filtration during and after pregnancy. The Journal of Obstetrics and Gynaecology of the British Commonwealth 81: 588–595 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Davison, J.S.; Davison, M.C. and Hay, D.M.: Gastric emptying time in late pregnancy and labour. The Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 37–41 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Depp, R.; Kind, A.C.; Kirby, W.M. and Johnson, W.: Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid. American Journal of Obstetrics and Gynecology 107: 1054–1057 (1970).

    PubMed  CAS  Google Scholar 

  • Dettli, L.: Elimination kinetics and drug dosage in renal insufficiency patients. Triangel 14: 117–123 (1975).

    CAS  Google Scholar 

  • Dettli, L.: Elimination kinetics and dosage adjustment of chemotherapeutic agents in patients with kidney disease. In press.

  • Dettli, L. and Spring, P.: The modifying effect of physiological variables and disease upon pharmacokinetics in Pharmacology and the future of man. Proceeding of the 5th International Congress of Pharmacology, San Francisco, 1972, Vol. 3: 165–173 (Karger, Basel, 1973).

    Google Scholar 

  • Duignan, N.M.; Andrews, J. and Williams, J.D.: Pharmacological studies with lincomycin in late pregnancy. British Medical Journal 3: 75–78 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Ehmebo, M.; Agurell, S.; Jailing, B. and Boreus, L.O.: Age differences in drug binding by plasma proteins: Studies on human fetuses, neonates and adults. European Journal of Clinical Pharmacology 3: 189–193 (1971).

    Article  Google Scholar 

  • Elliot, P.M. and Jaman, W.H.: Volume of liquor amnii in normal and abnormal pregnancy. Lancet 835 (1961).

  • Forfar, J.O. and Nelson, M.M.: Epidemiology of drugs taken by pregnant women: Drugs that may affect the fetus adversely. Clinical Pharmacology and Therapeutics 14: 632–642 (1973).

    PubMed  CAS  Google Scholar 

  • Fox, G.S.; Houle, G.L.; Desjardins, P.D. and Mercier, G.: Intrauterine fetal lidocaine concentration during continuous epidural anesthesia. American Journal of Obstetrics and Gynecology 110: 896–899 (1971).

    PubMed  CAS  Google Scholar 

  • Ganapathy, S.K. and Cohen, S.N.: Some physical and binding characteristics of human albumin from cord blood. Pediatric Research 9: 283 (1975).

    Google Scholar 

  • Ganshorn, A. and Kurz, H.: Unterschiede zwischen der Proteinbindung Neugeborener und Erwachsener und ihre Bedeutung fur die pharmakologische Wirkung. Naunyn-Schmiedebergs Archiv fur Pharmakologie und experimentelle Pathologie 260: 117–118 (1968).

    Article  CAS  Google Scholar 

  • Garrettson, L.K.; Procknal, J.A. and Levy, G.: Fetal acquisition and neonatal elimination of a large amount of salicylate. Clinical Pharmacology and Therapeutics 17: 98–103 (1975).

    PubMed  CAS  Google Scholar 

  • Gibaldi, M.: Effect of mode of administration on drug distribution in a two-compartment open system. Journal of Pharmaceutical Sciences 58: 327–331 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi, M. and Weintraub, H.: Some considerations as to the determination and significances of biologic half-life. Journal of Pharmaceutical Sciences 60: 624–626 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Ginsburg, J.: Placental drug transfer. Annual Review of Pharmacology 11: 387–408 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Ginsburg, J. and Duncan, S.L.B.: Peripheral blood flow in normal pregnancy. Cardiovascular Research 1: 132–137 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Gryboski, W.A. and Spiro, H.M.: The effect of pregnancy on gastric secretion. New England Journal of Medicine 255: 1131–1137 (1956).

    Article  PubMed  CAS  Google Scholar 

  • Harrison, L. and Gibaldi, M.: Influence of cholestasis on drug elimination: Pharmacokinetics. Journal of Pharmaceutical Sciences 65: 1346–1348 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Hermans, J.; Driessen, O.; Sorgedrager, N. and Spoor, M.: Pharmacokinetic analysis of ampicillin concentration in neonates. Arzneimittelforschung (Drug Research) 25: 947–949 (1975).

    CAS  Google Scholar 

  • Hill, R.M.: Drugs ingested by pregnant women. Clinical Pharmacology and Therapeutics 14: 654–659 (1973).

    PubMed  CAS  Google Scholar 

  • Hirsch, A.H.; Herbst, S.; Lang, R.; Dettli, L. and Gablinger, A.: Transfer of a new cephalosporin antibiotic to the fetus and the amniotic fluid during a continuous infusion (steady state) and single repeated intravenous injections to the mother. Arzneimittelforschung (Drug Research) 24: 1474–1478 (1974).

    CAS  Google Scholar 

  • Horning, M.G.; Stratton, C.; Nowlin, J.; Wilson, A.; Horning, E.C. and Hill, R.M.: Placental transfer of drugs; in: Boreus (Ed.): Fetal Pharmacology, p.355–372 (Raven Press, New York 1973).

    Google Scholar 

  • Hunt, J.N. and Murray, F.A.: Gastric function in pregnancy. The Journal of Obstetrics and Gynaecology of the British Empire 65: 78–83 (1958).

    Article  PubMed  CAS  Google Scholar 

  • Hytten, F.E. and Leitch, I.: The physiology of pregnancy, (Blackwell, Oxford 1971).

    Google Scholar 

  • Idanpaan-Heikkila, J.E.; Jouppila, P.I.; Poulakka, J.O. and Vorne, M.S.: Placental transfer and fetal metabolism of diazepam in early human pregnancy. American Journal of Obstetrics and Gynecology 109: 1011–1016 (1971).

    PubMed  CAS  Google Scholar 

  • Juchau, M.R.; Lee, Q.H.; Louviaux, G.L.; Symms, K.G.; Krasner, J. and Yaffe, S.J.: Oxidation and reduction of foreign compounds in tissues of the human placenta and fetus; in Boreus (Ed.) Fetal Pharmacology, p.321–353 (Raven Press, New York 1973).

    Google Scholar 

  • Juchau, M.R.: Drug biotransformation reactions in the placenta: in Mirkin (Ed.) Perinatal Pharmacology and Therapeutics, p.71–118 (Academic Press, New York 1976).

    Google Scholar 

  • Kerr, M.G.: Cardiovascular dynamics in pregnancy and labour. British Medical Bulletin 24: 19–24 (1968).

    Google Scholar 

  • Krauer, B.: Antibacterial therapy under special conditions: Paediatrics; in Schonfeld and Brockman (Eds.) Antibiotics and Chemotherapy, Vol. 18 p.89–111 (Karger, Basel 1974).

    Google Scholar 

  • Krauer, B.; Spring, P. and Dettli, L.: Zur Pharmakokinetik der Sulfonamide in ersten Lebensjahr. Pharmacologia Clinica 1: 47–53 (1968).

    Article  CAS  Google Scholar 

  • Le Blanc, A.L. and Perry, J.E.: Transfer of tetracycline across the placenta. Texas Reports on Biology and Medicine 25: 541–545 (1967).

    Google Scholar 

  • Lees, M.M.; Scott, D.B. and Kerr, M.G.: Haemodynamic changes associated with labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 29–36 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Lehmann, V.; Wettengel, R. and Hempelmann, G.: Untersuchungen zur Haemodynamik unter der Geburt. Zeitschrift fur Geburtshilfe und Perinatologie 176: 403–408 (1972).

    PubMed  CAS  Google Scholar 

  • Levy, G.: Salicylate pharmacokinetics in the human neonate; in Morselli, Garattini, and Sereni (Eds.) Basic and therapeutic aspects of perinatal pharmacology, p.319–330 (Raven Press, New York 1975).

    Google Scholar 

  • Levy, G. and Garrettson, L.K.: Kinetics of salicylate elimination by newborn infants of mothers who ingested aspirin before delivery. Pediatrics 53: 201–210 (1974).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Gibaldi, M.: Pharmacokinetics of drug action. Annual Review of Pharmacology 12: 85–98 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Levy, G.; Gibaldi, M. and Jusko, W.J.: Multicompartment pharmacokinetic models and pharmacological effects. Journal of Pharmaceutical Sciences 58: 422–424 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Levy, G. and Hayton, W.L.: Pharmacokinetic aspects of placental drug transfer; in Boreus (Ed.) Fetal Pharmacology, p.29–39 (Raven Press, New York 1973).

    Google Scholar 

  • Levy, G.; Procknal, J.A., and Garrettson, L.K.: Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clin. Pharmacol. Ther. 18: 210–214 (1975).

    CAS  Google Scholar 

  • Lewis, B.V.: Uterine blood flow. Obstetrical and Gynecological Survey 24: 1211–1233 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Mandelli, M.; Morselli, P.L.; Mordio, S.; Principi, N.; Sereni, F. and Tognono, G.: Placental transfer of diazepam and its disposition in the newborn. Clinical Pharmacology and Therapeutics 17: 564–572 (1975).

    PubMed  CAS  Google Scholar 

  • Mirkin, B.L.: Effects of drugs on the fetus and-neonate. Postgraduate Medicine 47: 91–95 (1970).

    PubMed  CAS  Google Scholar 

  • Mirkin, B.L. and Singh, S.: Placental transfer of pharmacologically active molecules; in Mirkin (Ed.) Perinatal Pharmacology and Therapeutics, p.1–69 (Academic Press, New York 1976).

    Google Scholar 

  • Morselli, P.L.: Clinical pharmacokinetics in neonates. Clinical Pharmacokinetics 1: 81–98 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Moya, F. and Thorndike, V.: Passage of drugs across the placenta. American Journal of Gynecology and Obstetrics 84: 1778–1798 (1962).

    CAS  Google Scholar 

  • Munnell, E.W. and Taylor, H.C.: Liver blood flow in pregnancy-hepatic vein catheterization. Journal of Clinical Investigation 26: 952–956 (1947).

    Article  PubMed  CAS  Google Scholar 

  • Murray, F.A.; Erskine, J.P. and Fielding, J.: Gastric secretion in pregnancy. The Journal of Obstetrics and Gynaecology of the British Empire 64: 373–381 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Noschel, H.; Bonow, A.; Muller, R.; Estel, Ch. and Muller, B.: Placentarpassage von Natriumsalicylat. Zentralblatt fur Gynakologie 94: 437–442 (1972).

    PubMed  CAS  Google Scholar 

  • Parry, E.; Shields, R. and Turnbull, A.C.: Transit time in the small intestine in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 900–901 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Peckham, C.H. and King, R.W.: A study of intercurrent conditions observed during pregnancy. American Journal of Obstetrics and Gynecology 87: 609–624 (1963).

    PubMed  CAS  Google Scholar 

  • Pelkonen, O.; Korhonen, P.; Jouppila, P. and Karki, N.T.: Placental transfer and fetal metabolism of drugs; in Morselli, Garattini and Sereni (Eds) Basic and therapeutic aspects of perinatal pharmacology, p.65–74 (Raven Press, New York 1975).

    Google Scholar 

  • Perry, J.E. and Leblanc, A.L.: Transfer of ampicillin across the human placenta. Texas Report on Biology and Medicine 25: 547–551 (1967).

    CAS  Google Scholar 

  • Pirani, B.B.K.; Campbell, D.M. and McGillivray, I.: Plasma volume in normal pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 80: 884–887 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Pitkin, R.M.; Reynolds, W.A.; Filer, L.J. and Kling, T.G.: Placental transmission and fetal distribution of saccharine. American Journal of Obstetrics and Gynecology 111: 280–286 (1971).

    PubMed  CAS  Google Scholar 

  • Prakash, A.; Chalmers, J.A.; Onojobi, O.I.A.; Henderson, R.J. and Cummings, P.: Transfer of limecycline and cephaloridine from mother to fetus — a comparative study. Journal of Obstetrics and Gynaecology of the British Commonwealth 77; 247–252 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.: Drug absorption interactions-gastric emptying; in Morselli, Cohen and Garattini (Eds) Drug Interactions, p.11–20 (Raven Press, New York 1974).

    Google Scholar 

  • Rane, A.: Urinary excretion of diphenyl hydantoin metabolites in newborn infants. Journal of Pediatrics 85: 543–545 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Rane, A.; Von Bahr, Chr.; Orrenius, S. and Sjoqvist, F.: Drug metabolism in the human fetus; in Boreus (Ed.) Fetal Pharmacology, p.287–301 (Raven Press, New York 1973).

    Google Scholar 

  • Rebond, P.; Groulade, J. and Groslambert, P.: The influence of normal pregnancy and the postpartum state on plasma proteins and lipids. American Journal of Obstetrics and Gynecology 86: 820–828 (1963).

    Google Scholar 

  • Robertson, E.G.: Physiological adjustments in pregnancy: Water Metabolism. Clinics in Obstetrics and Gynecology 2: 431–440 (1975).

    Google Scholar 

  • Sommer, K.R.; Hill, R.M. and Horning, M.G.: Identification and quantification of drugs in human amniotic fluid. Research Communications in Clinical Pathology and Pharmacology 12: 583–595 (1975).

    CAS  Google Scholar 

  • Stern, L.: Drug therapy in the perinatal period; in Morselli, Garattini and Sereni (Eds.) Basic and therapeutic aspects of perinatal pharmacology, p.7–12 (Raven Press, New York 1975).

    Google Scholar 

  • Templeton, A. and Kelman, G.R.: Maternal blood gases, physiological shunt and VD/VT in normal pregnancy. British Journal of Anaesthesiology 48: 1001–1004 (1976).

    Article  CAS  Google Scholar 

  • Tucker, G.T.; Boyes, R.N. and Bridenbaugh, P.O.: Binding of anilide-type local anesthetics in human plasma. II. Implications in vivo, with special reference to transplacental distribution. Anesthesiology 33: 304–314 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Ueland, K. and Hansen, J.M.: Maternal cardiovascular dynamics: Posture and uterine contractions. American Journal of Obstetrics and Gynecology 103: 1–7 (1969).

    PubMed  CAS  Google Scholar 

  • Labor and delivery under local and caudal analgesia. American Journal of Obstetrics and Gynecology 103: 8–18, (1969).

    Google Scholar 

  • Villee, Cl.A.: Placental transfer of drugs. Annals of New York Academy of Sciences 123: 237–242 (1965).

    Article  CAS  Google Scholar 

  • Von Kobyletzki, D.: Experimentelle Untersuchungen zur diaplazentaren Passage von Gentamycin. International Journal of Clinical Pharmacology 2: 116–119 (1967).

    Google Scholar 

  • Walters, W.A.W. and Leng Ling, Y.: Blood volume and haemodynamics in pregnancy; in Obstetrics and Gynecology: Vol. 2, p.301–302 (Saunders, London 1975).

    Google Scholar 

  • Wilkinson, G.R.: Pharmacokinetics of drug disposition: Hemodynamic considerations. Annual Review of Pharmacology 1 5: 11–27 (1975).

    Article  Google Scholar 

  • Wright, H.P.; Osborn, S.B. and Edmonds, D.G.: Changes in the flow of venous blood in the leg during pregnancy. Surgery, Gynecology and Obstetrics 90: 481–485 (1950).

    Google Scholar 

  • Yaffe, S.J. and Juchau, M.R.: Perinatal pharmacology. Annual Review of Pharmacology 14: 219–238 (1974).

    Article  CAS  Google Scholar 

  • Yaffe, S.J.; Rane, A. and Sjoqvist, F.: The presence of mono-oxygenase system in human fetal liver microsomes. Life Sciences 9: 1189–1200 (1970).

    Article  CAS  Google Scholar 

  • Yaffe, S.J. and Stern, L.: Clinical implications of perinatal pharmacology; in Mirkin (Ed.) Perinatal pharmacology and therapeutics, p.355–428 (Academic Press, New York 1976).

    Google Scholar 

  • Young, I.M.: The Placenta: Blood flow and transfer; in Modern Trends in Physiology, p.214–244 (Butterworths, London 1972).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University Hospital, 20, rue Alcide-Jentzer, 1205, Geneva, Switzerland

    Beatrice Krauer & F. Krauer

Authors
  1. Beatrice Krauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Krauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krauer, B., Krauer, F. Drug Kinetics in Pregnancy. Clin Pharmacokinet 2, 167–181 (1977). https://doi.org/10.2165/00003088-197702030-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197702030-00002

Keywords

Search

Navigation