Summary
Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses.
Accumulated data for several β-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micro-organisms are less likely to be affected.
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References
Alexanderson, B.: Prediction of steady-state plasma levels of nortriptyline from single oral dose kinetics: a study in twins. European Journal of Clinical Pharmacology 6: 44–53 (1973).
Amon, K.; Amon, I. and Huller, H.: Verteilung und Kinetik von Nitrofurantoin in der Fruhschwangerschaft. International Journal of Clinical Pharmacology, Therapy and Toxicology 63: 218–222 (1972).
Barr, W. and Graham, R.: Placental transmission of cephaloridine. Postgraduate Medical Journal 43 (Suppl): 101–104 (1967).
Bastert, G.; Muller, W.G.; Wallhauser, K.H. and Hebauf, H.: Pharmacokinetische Untersuchungen zum Ubertritt von Antibiotika in das Fruchtwasser am Ende der Schwangerschaft. 3. Teil: Oxacillin. Zeitschrift fur Geburtshilfe und Perinatologie 179: 346–355 (1975).
Bastert, G.; Wallhauser, K.H.; Wernicke, K. and Muller, W.G.: Pharmakokinetische Untersuchungen zum Ubertritt von Antibiotika in das Fruchtwasser am Ende der Schwangerschaft 1. Teil: Ampicillin. Zeitschrift fur Geburtshilfe und Perinatologie 177: 330–339 (1973).
Bastert, G.; Wernicke, K.; Muller, W.-G. and Hebauf, H.: Pharmakokinetische Untersuchungen zum Ubertritt von Antibiotika in das Fruchtwasser am Ende der Schwangerschaft. 2. Teil: Cephalothin. Zeitschrift fur Geburtshilfe und Perinatologie 178: 164–173 (1974).
Bernard, B.; Abate, M.; Thielen, P.F.; Attar, H.; Ballard, C.A. and Wehrte, P.F.: Maternal-fetal pharmacological activity of amikacin. The Journal of Infectious Diseases 135: 925–932 (1977a).
Bernard, B.; Barton, L.; Abate, M. and Ballard, C.A.: Maternal-fetal transfer of cefazolin in the first twenty weeks of pregnancy. The Journal of Infectious Diseases 136: 377–382 (1977b).
Bernard, B.; Garcia-Cazares, S.J.; Ballard, C.A.; Thrupp, L.D.; Mathies, A.W. and Wehrle, P.F.: Tobramycin: maternal-fetal pharmacology. Antimicrobial Agents and Chemotherapy 11: 688–694 (1977c).
Bernard, B.; Thielen, P.; Garcia-Cazares, S.J. and Ballard, C.A.: Maternal-fetal pharmacology of cefatrizine in the first 20 weeks of pregnancy. Antimicrobial Agents and Chemotherapy 12: 231–236 (1977d).
Boreus, L.O.: Placental transfer of ampicillin in man. Acta Pharmacologica et Toxicologica Suppl. 3: 250–254 (1971).
Bray, R.E.; Boe, R.W. and Johnson, W.L.: Transfer of ampicillin into fetus and amniotic fluid from maternal plasma in late pregnancy. American Journal of Obstetrics and Gynecology 96: 938–942 (1966).
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).
Daubenfeld, O.; Modde, H. and Hirsch, H.A.: Transfer of gentamicin to the foetus and the amniotic fluid during a steady state in the mother. Archiv fur Gynakologie 217: 233–240 (1974).
Depp, R.; Kind, A.C.; Kirby, W.M.M. and Johnson, W.L.: Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid. American Journal of Obstetrics and Gynecology 107: 1054–1057 (1970).
Dornbusch, K.: State Bacteriological Laboratory, Stockholm, Sweden (Personal communication).
Duval, J.; Mora, M.; Chartier, M. and Mansour, N.: La Cephalexine. Son transfert placentaire. La Nouvelle Presse Medicale I: 1419–1420 (1972).
Eadie, M.J.; Lander, C.M. and Tyrer, J.H.: Plasma drug level monitoring in pregnancy. Clinical Pharmacokinetics 2: 427–436 (1977).
Ehrnebo, M.; Agurell, S.; Jailing, B. and Boreus, L.O.: Age differences in drug binding by plasma proteins: Studies on human foetuses, neonates and adults. European Journal of Clinical Pharmacology 3: 189–193 (1971).
Feuer, G. and Kardish, R.: Hormonal regulation of drug metabolism during pregnancy. International Journal of Clinical Pharmacology 11: 366–374 (1975).
Good, R.G. and Johnson, G.: The placental transfer of kanamycin during later pregnancy. Obstetrics and Gynecology 38: 60–62 (1971).
Gut, I.; Becker, B.A. and Gutova, M.: Effect of pregnancy on hepatic microsomal drug metabolism in rabbits and rats. Archives of Toxicology 35: 41–47 (1976).
Hirsch, H.A.; Dreher, E.; Perrochet, A. and Schmid, E.: Transfer of ampicillin to the fetus and amniotic fluid during continuous infusion (steady state) and by repeated single intravenous injections to the mother. Infection 2: 207–212 (1974a).
Hirsch, H.A.; Herbst, S.; Lang, R.; Dettli, L. and Gablinger, A.: Transfer of a new cephalosporin antibiotic to the foetus and the amniotic fluid during a continuous infusion (steady state) and single repeated intravenous injections to the mother. Archiv fur Gynakologie 216: 1–14 (1974b).
Hytten, F.E. and Leiten, I.: The Physiology of Human Pregnancy, 2nd ed (Blackwell Scientific Publications, Oxford, London, Edinburgh 1971).
Krauer, B. and Krauer, F.: Drug kinetics in pregnancy. Clinical Pharmacokinetics 2: 167–181 (1977).
MacAulay, M.A.; Abou-Sabe, M. and Charles, D.: Placental transfer of ampicillin. American Journal of Obstetrics and Gynecology 96: 943–950 (1966).
MacAulay, M.A.; Berg, S.R. and Charles, D.: Placental transfer of dicloxacillin at term. American Journal of Obstetrics and Gynecology 102: 1162–1168 (1968).
MacAulay, M.A. and Charles, D.: Placental transfer of cephalothin. American Journal of Obstetrics and Gynecology 100: 940–946 (1968).
MacAulay, M.A.; Molloy, W.B. and Charles, D.: Placental transfer of methicillin. American Journal of Obstetrics and Gynecology 115: 58–65 (1973).
Mirkin, B.L.: Perinatal pharmacology: placental transfer, fetal localization, and neonatal disposition of drugs. Anesthesiology 43: 156–170 (1975).
Morrow, S.; Palmisano, P. and Cassady, G.: The placental transfer of cephalothin. The Journal of Pediatrics 73: 262–264 (1968).
Paterson, L.; Henderson, A.; Burnett Lunan, C. and McGurk, S.: Transfer of cephalothin sodium to the fetus. The Journal of Obstetrics and Gynaecology of the British Commonwealth 77: 565–566 (1970).
Perry, J.E. and Leblanc, A.L.: Transfer of ampicillin across the human placenta. Texas Reports on Biology and Medicine 25: 547–551 (1967).
Philipson, A.: Pharmacokinetics of ampicillin during pregnancy. The Journal of Infectious Diseases 136: 370–376 (1977).
Philipson, A.: Plasma levels of ampicillin in pregnant women following administration of ampicillin and pivampicillin. American Journal of Obstetrics and Gynecology 130: 674–683 (1978).
Philipson, A.; Sabath, L.D. and Charles, D.: Transplacental passage of erythromycin and clindamycin. New England Journal of Medicine 288: 1219–1221 (1973).
Philipson, A.; Sabath, L.D. and Charles, D.: Erythromycin and clindamycin absorption and elimination in pregnant women. Clinical Pharmacology and Therapeutics 19: 68–77 (1976).
Plomp, T.A.; Maes, R.A.A.; Thiery, M. and Yo Le Sian, A.: Placental transfer of thiamphenicol. Zeitschrift fur Geburtshilfe und Perinatalogie 180: 149–156 (1976).
Pruitt, A.W. and Dayton, P.G.: A comparison of the binding of drugs to adult and cord plasma. European Journal of Clinical Pharmacology 4: 59–62 (1971).
Reid, D.W.J.; Caille, G. and Kaufmann, N.R.: Maternal and transplacental kinetics of trimethoprim and sulfamethoxazole, separately and in combination. Canadian Medical Association Journal 112(13): 67S–72S (1975).
von Voigt, R.; Schroder, S.; Meinhold, P.; Zenner, I. and Noschel, H.: Klinische Untersuchungen zum Einfluss von Schwangerschaft und Geburt auf die Pharmakokinetik von Ampizillin. Zentralblatt fur Gynakologie 100: 701–705 (1978).
Walter, A.M. and Heilmeyer, L.: Antibiotika-Fibel. 4. Auflage. (Georg Thieme Verlag, Stuttgart 1975).
Weinstein, A.J.; Gibbs, R.S. and Gallagher, M.: Placental transfer of clindamycin and gentamicin in term pregnancy. American Journal of Obstetrics and Gynecology 124: 688–691 (1976).
Ylikorkala, O.; Sjostedt, E.; Jarvinen, P.A.; Tikkanen, R. and Raines, T.: Trimethoprim-sulfonamide combination administered orally and intravaginally in the first trimester of pregnancy: its absorption into serum and transfer to amniotic fluid. Acta Obstetrica et Gynecologica Scandinavica 52: 229–234 (1973).
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Philipson, A. Pharmacokinetics of Antibiotics in Pregnancy and Labour. Clin Pharmacokinet 4, 297–309 (1979). https://doi.org/10.2165/00003088-197904040-00003
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DOI: https://doi.org/10.2165/00003088-197904040-00003