Clinical Pharmacokinetics

, Volume 33, Issue 5, pp 328–343 | Cite as

Pharmacokinetic Changes During Pregnancy and Their Clinical Relevance

  • Ronen Loebstein
  • Arieh Lalkin
  • Gideon Koren
Review Article Special Populations


The dynamic physiological changes that occur in the maternal-placental-fetal unit during pregnancy influence the pharmacokinetic processes of drug absorption, distribution and elimination. Pregnancy-induced maternal physiological changes may affect gastrointestinal function and hence drug absorption rates. Ventilatory changes may influence the pulmonary absorption of inhaled drugs.

As the glomerular filtration rate usually increases during pregnancy, renal drug elimination is generally enhanced, whereas hepatic drug metabolism may increase, decrease or remain unchanged. A mean increase of 8L in total body water alters drug distribution and results in decreased peak serum concentrations of many drugs. Decreased steady-state concentrations have been documented for many agents as a result of their increased clearance.

Pregnancy-related hypoalbuminaemia, leading to decreased protein binding, results in increased free drug fraction. However, as more free drug is available for either hepatic biotransformation or renal excretion, the overall effect is an unaltered free drug concentration. Since the free drug concentration is responsible for drug effects, the above mentioned changes are probably of no clinical relevance. The placental and fetal capacity to metabolise drugs together with physiological factors, such as differences acid-base equilibrium of the mother versus the fetus, determine the fetal exposure to the drugs taken by the mother.

As most drugs are excreted into the milk by passive diffusion, the drug concentration in milk is directly proportional to the corresponding concentration in maternal plasma. The milk to plasma (M : P) ratio, which compares milk with maternal plasma drug concentrations, serves as an index of the extent of drug excretion in the milk. For most drugs the amount ingested by the infant rarely attains therapeutic levels.


Pregnant Woman Adis International Limited Digoxin Valproic Acid Breast Milk 
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  1. 1.
    Heinonen OP, Slone D, Monson RR, et al. Cardiovascular birth defects and antenatal exposure to female sex hormones. N Engl J Med 1977; 296(2): 60–7Google Scholar
  2. 2.
    Forfal JO, Nelson MM. Epidemiology of drugs taken by pregnant women: drugs that may affect the fetus adversly. Clin Pharmacol Ther 1973; 14: 632–42Google Scholar
  3. 3.
    Brocklebank JC, Ray WA, Federspiel CF, et al. Drug prescribing during pregnancy: a controlled study of Tenessee Medicaid recepients. Am J Obstet Gynecol 1978; 132(3): 235–44PubMedGoogle Scholar
  4. 4.
    Cordero JF, Oakley GP. Drug exposure during pregnancy: some epidemiologic considerations. Clin Obstet Gynecol 1983; 26(2): 418–28PubMedGoogle Scholar
  5. 5.
    Piper JM, Baum C, Kennedy DL. Prescription drug use before and during pregnancy in a Medicaid population. Am J Obstet Gynecol 1987; 157(1): 148–56PubMedGoogle Scholar
  6. 6.
    Hytten FE, Leitch T. The physiology of pregnancy. Oxford: Blackwell, 1971Google Scholar
  7. 7.
    Quilligan EJ, Kaiser IH. Maternal physiology. In: Danforth DN, editor. Danforth obstetrics and gynecology. 3rd ed. New York: Harper and Row, 1982: 326–41Google Scholar
  8. 8.
    Young IM. The placenta: blood flow and transfer. In: Downman CBB, editor. Modern trends in physiology. London: Butterworth, 1972: 214–44Google Scholar
  9. 9.
    Mirkin BL, Singh S. Placental transfer of pharmacologically active molecules. In: Mirkin BL, editor. Perinatal pharmacology and therapeutics. New York: Academic Press, 1976: 1–69Google Scholar
  10. 10.
    Krauer B, Krauer F. Drug kinetics in pregnancy. In: Gibaldi M, Prescott L, editors. Handbook of clinical pharmacokinetics. New York: Adis, 1983: 1–17Google Scholar
  11. 11.
    Parry E, Shields R, Turnbull A. Transit time in the small intestine in pregnancy. J Obstet Gynaecol Br Commonw 1970; 77: 900–1PubMedGoogle Scholar
  12. 12.
    Hume Jr RF, Killam AP. Maternal physiology. In: Danforth DN. Obstetric and gynecology. 6th ed. Philadelphia: J.B. Lippincot Company, 1990: 93–100Google Scholar
  13. 13.
    Cugell DW, Frank NR, Gaensler EA, et al. Pulmonary function in pregnancy. Am Rev Tuberculosis 1953; 67: 568–97Google Scholar
  14. 14.
    Kerr MG. Cardiovascular dynamics in pregnancy and labour. Br Med Bull 1968; 24: 19–24Google Scholar
  15. 15.
    Palahniuk RJ, Shnider SM, Eger EI. Pregnancy decreases the requirement for inhaled anesthetic agents. Anesthesiology 1974; 41: 82–3PubMedGoogle Scholar
  16. 16.
    Pizani BBK, Campbell DM, McGillivray T. Plasma volume in normal pregnancy. J Obstet Gynaecol 1973; 80: 884–7Google Scholar
  17. 17.
    Dunihoo DR. Maternal physiology. In: Dunihoo DR, editor. Fundamentals of gynecology and obstetrics. Philadelphia: J.B. Lippincott Co., 1992: 280–4Google Scholar
  18. 18.
    Assali NS, Rauramot L, Peltonen T. Measurment of uterine blood flow and uterine metabolism. Am J Obstet Gynecol 1960; 79: 86–98PubMedGoogle Scholar
  19. 19.
    Dean M, Stock B, Patterson RJ, et al. Serum protein binding of drugs during and after pregnancy in humans. Clin Pharmacol Ther 1980; 28: 253–60PubMedGoogle Scholar
  20. 20.
    Wood M, Alastair JJ, Wood MB. Changes in plasma drug binding and α1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther 1981; 29: 522–6PubMedGoogle Scholar
  21. 21.
    Davis M, Simmons CJ, Dordini B, et al. Induction of hepatic enzymes during normal pregnancy. J Obstet Gynaecol Br Commonw 1973; 80: 690–94PubMedGoogle Scholar
  22. 22.
    Juchau MR, Mirkin DL, Zachariah PK. Interactions of various 19-nor steroids with human placental microsomal cytochrome P-450. Chem Biol Interact 1976; 15(4): 337–47PubMedGoogle Scholar
  23. 23.
    Harrison LI, Gibaldi M. Influence of cholestasis on drug elimination: pharmacokinetics. J Pharm Sci 1976; 65: 1246–348Google Scholar
  24. 24.
    Dettli L. Elimination kinetics and drug dosage in renal insuficiency patients. Triangle 1975; 14(3–4): 117–23PubMedGoogle Scholar
  25. 25.
    Davidson JM, Hytten FE. Glomerular filtration during and after pregnancy. J Obstet Gynaecol 1974; 81: 588–95Google Scholar
  26. 26.
    Koren G, Bologa M, Pastuszak A. The way women perceive a teratogenic risk: the decision to terminate pregnancy. In: Koren G, editor. Maternal-fetal toxcicology. 2nd ed. New York: Marcel Dekker Inc., 1994: 727–35Google Scholar
  27. 27.
    Levy G, Procknal JA, Garrettson LK. Distribution of salycilate between neonatal and maternal serum at diffusion equilibrium. Clin Pharmacol Ther 1975; 18(2): 210–4PubMedGoogle Scholar
  28. 28.
    Levy G. Salicylate pharmacokinetics in the human neonate. In: Morselli P, Garattini C, Sereni Y, editors. Basic and therapeutic aspects of perinatal pharmacology. New York: Raven Press, 1975: 319–30Google Scholar
  29. 29.
    Mandelli M, Morselli PL, Nordio S, et al. Placental transfer of diazepam and its disposition in the newborn. Clin Pharmacol Ther 1975; 17(5): 564–72PubMedGoogle Scholar
  30. 30.
    Bray RE, Boe RW, Johnson WL. Transfer of ampicillin into fetus and amniotic fluid from maternal plsma in late pregnancy. Am J Obstet Gynecol 1966; 96: 938–42PubMedGoogle Scholar
  31. 31.
    Dancis J, Braverman N, Lind J. Plasma protein synthesis in the human fetus and placenta. J Clin Invest 1957; 36: 398–404PubMedGoogle Scholar
  32. 32.
    Koren G. Changes in drug disposition in pregnancy and their clinical implications In: Koren G, editor. Maternal-fetal toxicology. 2nd ed. New York: Marcel Dekker Inc., 1994: 1–13Google Scholar
  33. 33.
    Juchau MR, Chao ST, Omiecinski CJ. Drug metabolism by the human fetus. In: Gibaldi M, Prescott L, editors. Handbook of clinical pharmacokinetics. New York: Adis, 1983: 58–78Google Scholar
  34. 34.
    Pelkonen O. Drug metabolism in the human fetal liver: relationship to fetal age. Arch Int Pharmacodyn Ther 1973; 202(2): 281–7PubMedGoogle Scholar
  35. 35.
    Pelkonen O, Karki NT. Demonstration of cytochrome P-450 in human foetal liver microsomes in early pregnancy. Acta Pharmacol Toxicol (Copenh) 1971; 30(1): 158–60Google Scholar
  36. 36.
    Derewlany LO, Leeder JS, Kumar R, et al. The transport of digoxin across the perfused human placental lobule. J Pharmacol Exp Ther 1991; 256(3): 1107–11PubMedGoogle Scholar
  37. 37.
    Binienda Z, Bailey JR, Duhart HM, et al. Transplacental pharmacokinetics and maternal/fetal plasma concentrations of cocaine in pregnant macaques near term. Drug Metab Dispos 1993; 21(2): 364–8PubMedGoogle Scholar
  38. 38.
    Schmidt D. The effect of pregnancy on the natural history of epilepsy. In: Janz D, Bossi L, Dam M, editors. Epilepsy, pregnancy and the child. New York: Raven Press, 1981: 3–14Google Scholar
  39. 39.
    Niebyl JR, Blake DA, Freeman JM, et al. Carbamazepine levels in pregnancy and lactation. Obstet Gynecol 1970; 53: 139–40Google Scholar
  40. 40.
    Brodie MJ. Established anticonvulsants and treatment of refractory epilepsy. Lancet 1990; 336: 350–4PubMedGoogle Scholar
  41. 41.
    Hanson JW, Smith DW. The fetal hydantoin syndrome. J Pediatr 1975; 89: 662–8Google Scholar
  42. 42.
    Howe AM, Lipson AH, Sheffield LJ, et al. Prenatal exposure to phenytoin: facial development and a possible role for vitamin K. Am J Med Genet 1995; 58(3): 238–44PubMedGoogle Scholar
  43. 43.
    Robert E, Guibaud P. Maternal valproic acid and congenital neural tube defects [letter]. Lancet 1982; 2: 937PubMedGoogle Scholar
  44. 44.
    Valproate: a new cause of birth defects: report from Italy and follow-up from France. MMWR Morb Mortal Wkly Rep 1983; 32: 438–9Google Scholar
  45. 45.
    Thomson AH, Brodie MJ. Pharmacokinetics optimisation of anticonvulsant therapy. Clin Pharmacokinet 1992; 23(3): 216–30PubMedGoogle Scholar
  46. 46.
    Yerby MS, Friel PN, Miller DQ. Carbamazepine binding and disposition in pregnancy. Ther Drug Monit 1985; 7: 269–73PubMedGoogle Scholar
  47. 47.
    Thomson T, Almkvist O, Nilsson BY, et al. Carbamazepine-10,11-epoxide in epilepsy: a pilot study. Arch Neurol 1990; 47: 888–92Google Scholar
  48. 48.
    Armijo JA, Cavanda E. Graphic estimation of phenytoin dose in adults and children. Ther Drug Monit 1991; 13: 507–10PubMedGoogle Scholar
  49. 49.
    Brodie MJ. Management of epilepsy during pregnancy and lactation. Lancet 1990; 336: 426–7PubMedGoogle Scholar
  50. 50.
    Perucca E, Richens A, Ruprah M. Serum protein binding of phenytoin in pregnant women. Proc Br Pharmacol Soc 1981; 11: 409P–10PGoogle Scholar
  51. 51.
    Chamberlain A, White S, Bawdon R, et al Pharmacokinetics of ampicillin and salmactam in pregnancy. Am J Obstet Gynecol 1993; 168: 667–73PubMedGoogle Scholar
  52. 52.
    Philipson A, Stiernstede G. Pharmacokinetics of cefuroxime in pregnancy. Am J Obstet Gynecol 1982; 142: 823–8PubMedGoogle Scholar
  53. 53.
    Heikkila A, Renkonen OV, Erkkola R. Pharmacokinetics and placental passage of imipenem during pregnancy. Antimicrob Agents Chemother 1992; 36: 2652–5PubMedGoogle Scholar
  54. 54.
    Voigt R, Schroder S, Peiker G. Pharmacokinetic studies of azlocillin and piperacillin during late pregnancy. Chemotherapy 1985; 31: 417–24PubMedGoogle Scholar
  55. 55.
    Barton JR, Prevost RR, Wilson DA, et al. Nifedipine pharmacokinetics and pharmacodynamics during the immediate postpartum period in patients with pre-eclampsia. Am J Obstet Gynecol 1991; 165: 951–4PubMedGoogle Scholar
  56. 56.
    Rogers RC, Sibai BM, Whybrew WD. Labetolol pharmacokinetics in pregnancy-induced hypertension. Am J Obstet Gynecol 1990; 162(2): 362–6PubMedGoogle Scholar
  57. 57.
    O’Hara MF, Leahey W, Murraghan GA, et al. Pharmacokinetics of sotalol during pregnancy. Eur J Clin Pharmacol 1983; 24(4): 521–4Google Scholar
  58. 58.
    Bologa M, Tang B, Klein J, et al. Pregnancy-induced changes in drug metabolism in epileptic women. J Pharmacol Exp Ther 1991; 257(2): 735–40PubMedGoogle Scholar
  59. 59.
    Henviksen O, Johannessen SI. Clinical and pharmacokinetic observations on sodium valproate: a five year follow-up study of 100 children with epilepsy. Acta Neurol Scand 1982; 65: 504–23Google Scholar
  60. 60.
    Pugh CB, Garnett WR. Current issues in the treatment of epilepsy. Clin Pharm 1991; 10: 335–58PubMedGoogle Scholar
  61. 61.
    Heikkila A, Erkkola R. Review of β-lactam antibiotic in pregnancy. Clin Pharmacokinet 1994; 27(1): 49–62PubMedGoogle Scholar
  62. 62.
    Schentag JJ, Smith IL, Swanson DJ, et al. Role for individualization with cefmenoxime. Am J Med 1984; 77Suppl. 6a: 43–50PubMedGoogle Scholar
  63. 63.
    Bergan T. Pharmacokinetics of tissue penetration of antibiotics. Rev infect Dis 1981; 3: 45–66PubMedGoogle Scholar
  64. 64.
    Barza M. Principles of tissue penetrations of antibiotics. J Antimicrob Chemother 1981; 8Suppl. C: 7–28PubMedGoogle Scholar
  65. 65.
    Schentag JJ. Clinical significance of antibiotic tissue penetration. Clin Pharmacokinet 1989; 16Suppl. 1: 25–31PubMedGoogle Scholar
  66. 66.
    Craig WA, Welling PG. Protein binding of antimicrobials: clinical pharmacokinetic and therapeutic implication. Clin Pharmacokinet 1977; 2: 252–68PubMedGoogle Scholar
  67. 67.
    Wise R, Gillet AP, Cadge B, et al. The influence of protein binding upon tissue fluid levels of six beta-lactams. J Infect Dis 1980; 142: 77–82PubMedGoogle Scholar
  68. 68.
    Drusano GL, Standiford HC, Bustamante C, et al. Multiple dose pharmacokinetics of imipenem/cilastatin (MK-787/MK-791). Antimicrob Agents Chemother 1984; 26: 715–21PubMedGoogle Scholar
  69. 69.
    Jones HM, Cummings AJ. A study of the transfer of alfamethyl dopa to the human foetus and nerborn infant. Br J Clin Pharmacol 1978; 6: 432–4PubMedGoogle Scholar
  70. 70.
    Kyegombe D, Franklin C, Turner P. Drug-metabolising enzymes in the human placenta, there induction and repression. Lancet 1973; I: 405–6Google Scholar
  71. 71.
    Pelkonen O. Xenibiotic metabolism in the maternal-placentalfetal unit: implications for fetal toxicity. Dev Pharmacol Ther 1984; 1Suppl. 7: 11–7Google Scholar
  72. 72.
    Philipson A. Pharmacokinetics of ampicillin during pregnancy. J Infect Dis 1977; 136:370–6PubMedGoogle Scholar
  73. 73.
    Boreus L-O. Placental transfer of ampicillin in man. Acta Pharmacol Toxicol (Copenh) 1971; 3 Suppl.: 250–4Google Scholar
  74. 74.
    Bastert G, Wallhauser K, Wernicke K, et al. Pharmacokinetische Untersuchungen zum Ubertritt von Antibiotica in das Fruchtwasser am Ende der Schwangerschaft: I. Teil: Ampicillin. Z Geburtshilfe Perinatol 1973; 178: 164–73Google Scholar
  75. 75.
    Voigt R, Schroder S, Meinhold P, et al. Klinische Untersuchungen zum einfluss von Schwangerschaft und geburt auf die Pharmacokinetik von Ampizillin. Zentralbl Gynakol 1978; 100: 701–5PubMedGoogle Scholar
  76. 76.
    Kubacka R, Johnstone H, Tan H, et al. Intravenous ampicillin pharmacokinetics in the third trimester of pregnancy. Ther Drug Monit 1983; 5: 55–60PubMedGoogle Scholar
  77. 77.
    Adamkin DH, Marshall E, Weiner LB. The placental transfer of ampicillin. Am J Perinatol 1984; 1: 310–1PubMedGoogle Scholar
  78. 78.
    Lang R, Shalit I, Segal J. Maternal and fetal serum and tissue levels of ceftriaxone following preoperative prophylaxis in emergency caesarean section. Chemotherapy 1993; 39: 77–81PubMedGoogle Scholar
  79. 79.
    Depp R, Kind AC, Kirby WMN, et al. Transplacental passage of methicillin and dicloxacillin into the fetus and amniotic fluid. Am J Obstet Gynecol 1970; 107: 1054–7PubMedGoogle Scholar
  80. 80.
    Daubenfeld O, Modde H, Hirsch HA. Transfer of gentamycin to the foetus and amniotic fluid during a steady state in the mother. Arch Gynecol 1974; 217: 233–40Google Scholar
  81. 81.
    Yoshioka H, Monma T, Matsudo S. Placental transfer of gentamycin. J Pediatr 1972; 80: 121–3PubMedGoogle Scholar
  82. 82.
    Heikkila A, Erkkola R. The need for adjustment of dosage regimen for penicillin V during pregnancy. Obstet Gynecol 1993; 81(6): 919–21PubMedGoogle Scholar
  83. 83.
    Wasz-Hockert O, Nummi S, Vuopala S, et al. Transplacental passage of azidocillin, ampicillin and penicillin during early and late pregnancy. Scand J Infect Dis 1970; 2: 125–30PubMedGoogle Scholar
  84. 84.
    Heikkila A, Erkkola R. Pharmacokinetics of piperacillin during pregnancy. J Antimicrob Chemother 1991; 28: 419–23PubMedGoogle Scholar
  85. 85.
    Martens MG, Faro S, Feldman S, et al. Pharmacokinetics of the acyclureidopenicillins piperacillin and mezlocillin in the postpartum patient. Antimicrob Agents Chemother 1987; 31: 2015–7PubMedGoogle Scholar
  86. 86.
    Begue P, Quinet B, Baron S, et al. Clinical and pharmacokinetic study of imipenem/cilastatin in children and newborn infants. Pathol Biol 1989; 5: 485–90Google Scholar
  87. 87.
    Duval J, Mora M, Chartier M, et al. La cephalexine: son transfer placentaire. Nouv Presse Med 1972; 1: 1419–20PubMedGoogle Scholar
  88. 88.
    MacAulay MA, Charles D. Placental transfer of cephalotin. Am J Obstet Gynecol 1968; 100: 940–6PubMedGoogle Scholar
  89. 89.
    Bernard B, Barton L, Abate M, et al. Maternal-fetal transfer of cefazolin in the first twenty weeks of pregnancy. J Infect Dis 1977; 136: 377–82PubMedGoogle Scholar
  90. 90.
    Kafetzis DA, Brater CD, Fanourgakis JE, et al. Ceftriaxone distribution between maternal blood and fetal blood and tissues at parturition and between blood and milk post partum. Antimicrob Agents Chemother 1983; 23: 870–3PubMedGoogle Scholar
  91. 91.
    Bourget D, Fernandez H, Quinquis V, et al. Pharmacokinetics and protein binding of ceftriaxone during pregnancy. Antimicrob Agents Chemother 1993; 37(1): 54–9PubMedGoogle Scholar
  92. 92.
    Schou M, Amidsen A, Steenstrup DR. Lithium and pregnancy: hazards to women given lithium during pregnancy and delivery. BMJ 1973; 2: 137–8PubMedGoogle Scholar
  93. 93.
    Rogers ME, Willerson JT, Goldblatt A, at al. Serum digoxin concentrations in the human fetus, neonate and infant. N Engl J Med 1972; 287: 1010–3PubMedGoogle Scholar
  94. 94.
    Butters L, Kennedy S, Rubon P. Atenolol in essential hypertension during pregnancy. BMJ 1990; 301: 587–9PubMedGoogle Scholar
  95. 95.
    Thorley KJ, McAinsh J, Cruickshank JM. Atenolol in the treatment of pregnancy-induced hypertension. Br J Clin Pharmacol 1981; 12: 725–30PubMedGoogle Scholar
  96. 96.
    Magee LA, Schick B, Donnenfeld AE, et al. The safety of calcium channel blockers in human pregnancy: a prospective, multicenter cohort study. Am J Obstet Gynecol 1996; 174: 823–8PubMedGoogle Scholar
  97. 97.
    Todd EL, Stafford DT, Bucovaz ET, et al. Pharmacokinetics of meperidine in pregnancy. Int J Gynaecol Obstet 1989; 29(2): 143–6PubMedGoogle Scholar
  98. 98.
    Martinez GA, Krieger FW. 1984 milk-feeding patterns in the United States. Pediatrics 1985; 76: 1004–8PubMedGoogle Scholar
  99. 99.
    McNally E, Hendricks S, Horowitz I. A look at breast-feeding trends in Canada (1963–1982). Can J Public Health 1985; 76: 101–7PubMedGoogle Scholar
  100. 100.
    Simopoulos AP, Grave GD. Factors associated with the choice and duration of infant-feeding practice. Pediatrics 1984; 74 (4 Pt 2): 603–14PubMedGoogle Scholar
  101. 101.
    Berlin CM. The excretion of drug and chemicals in human milk. In: Yaffe SJ, editor. Pediatric pharmacology: therapeutic principles in practice. New York: Grune & Stratton, 1980: 137–47Google Scholar
  102. 102.
    Kafetzis DA, Siafas CA, Georgakopoulos PA, et al. Passage of cephalosporins and amoxicillin into the breast milk. Acta Paediatr Scand 1981; 70: 285–8PubMedGoogle Scholar
  103. 103.
    Thorley KJ, McAinsh J. Levels of the beta-blockers atenolol and propranolol in the breast milk of women treated for hypertension in pregnancy. Biopharm Drug Dispos 1983; 4: 299–301PubMedGoogle Scholar
  104. 104.
    Schmimmel MS, Eidelman AJ, Wilschanski MA, et al. Toxic effects of atenolol consumed during breast feeding. J Pediatr 1989; 114:476–8PubMedGoogle Scholar
  105. 105.
    Froescher W, Eichelbaum M, Niesen M, et al. Carbamazepine levels in breast milk. Ther Drug Monit 1984; 6: 266–71PubMedGoogle Scholar
  106. 106.
    Wesson DR, Camber S, Harkey M, et al. Diazepam and desmethyldiazepam in breastmilk. J Psychoactive Drugs 1985; 17: 55–6PubMedGoogle Scholar
  107. 107.
    Loughnan PM. Digoxin excretion in human breast milk. J Pediatr 1978; 92: 1019–20PubMedGoogle Scholar
  108. 108.
    Sykes PA, Quarrie J, Alexander FW. Lithium carbonate and breast feeding. BMJ 1976; 2: 1299PubMedGoogle Scholar
  109. 109.
    Greene HJ, Burkhart B, Hobby GL, et al. Excretion of penicillin in human milk following parturition. Am J Obstet Gynecol 1946; 51: 732–3PubMedGoogle Scholar
  110. 110.
    Steen B, Rane A, Lonnerholm G, et al. Phenytoin excretion in human breast milk and plsma levels in nursed infants. Ther Drug Monit 1982; 4: 331–4PubMedGoogle Scholar
  111. 111.
    Yurchav AM, Jusco WJ. Theophylline secretion into breast milk. Pediatrics 1976; 57: 518–20Google Scholar
  112. 112.
    Orme ML’O, Lewis PJ, De Swiet M, et al. May mothers given warfarin breast-feed their infants? BMJ 1977; 1: 1564–5PubMedGoogle Scholar
  113. 113.
    Catz CS, Giacoia GP. Drugs and breast milk. Pediatr Clin North Am 1972; 19: 151–66PubMedGoogle Scholar
  114. 114.
    World Health Organization Working Group. Determinants of drug excretion in breast milk. In: Bennett PN, Matheson I, Dukes NMG, et al., editors. Drugs and human lactation. Amsterdam: Elsevier, 1988: 27–48Google Scholar
  115. 115.
    Wilson JT. Determinants and consequences of drug excretion in breast milk. Drug Metab Rev 1983; 14: 619–52PubMedGoogle Scholar
  116. 116.
    Atkinson HC, Begg EJ. Prediction of drug concentrations in human milk from plasma protein binding and acid-base characteristics. Br J Clin Pharmacol 1988; 25: 495–503PubMedGoogle Scholar
  117. 117.
    Ito S, Koren G. A novel index for expressing exposure of the infant to drugs in breast milk. Br J Clin Pharmacol 1994; 38: 99–102PubMedGoogle Scholar
  118. 118.
    Braverman LE. Iodine-induced thyroid disease. Acta Med Austriaca 1990; 17: 29–33PubMedGoogle Scholar
  119. 119.
    Kulski JK, Hartmann PE, Martin JD, et al. Effects of bromocriptine mesylate on the composition of the mammary secretion in non-breast-feeding women. Obstet Gynecol 1978; 52: 38–42PubMedGoogle Scholar
  120. 120.
    Katz M, Kroll D, Pak I, et al. Puerperal hypertention, stroke and seizures after suppression of lactation with bromocriptine. Obstet Gynecol 1985; 66: 822–4PubMedGoogle Scholar
  121. 121.
    Wiernik PH, Duncan JH. Cyclophosphamide in human milk. Lancet 1971; I: 912Google Scholar
  122. 122.
    Amato D, Niblett JS. Neutropenia from cyclophosphamide in breast milk [letter]. Med J Aust 1977; 1: 383–4PubMedGoogle Scholar
  123. 123.
    Fletcher SM, Katz AR, Rogers AJ, et al. The presence of cyclosporine in body tissue and fluids during pregnancy. Am J Kidney Dis 1985; 5: 60–3Google Scholar
  124. 124.
    Egan PC, Costanza ME, Dodion P, et al. Doxorubicin and cisplatin excretion into human milk. Cancer Treat Rep 1985; 69: 1387–9PubMedGoogle Scholar
  125. 125.
    Tegler L, Lindstrom B. Antithyroid drugs in milk [letter]. Lancet 1980; II: 591Google Scholar
  126. 126.
    Kampmann JP, Johansen K, Hansen JM, et al. Propylthiouracil in human milk: revision of a dogma. Lancet 1980; I: 736–7Google Scholar
  127. 127.
    Johansen K, Anderson AN, Kampmann JP, et al. Excretion of methimazole in human milk. Eur J Clin Pharmacol 1982; 23: 339–41PubMedGoogle Scholar
  128. 128.
    Cooper DS. Antithyroid drugs: to breast feed or not to breast feed. Am J Obstet Gynecol 1987; 157: 234–5PubMedGoogle Scholar
  129. 129.
    Von Unruh GE, Froescher W, Hoffman F, et al. Valproic acid in breast milk: how much is really there?Ther Drug Monit 1984; 6: 272–6Google Scholar
  130. 130.
    Kaneko S, Sato T, Suzuki K. The levels of anticonvulsants in breast milk. Br J Clin Pharmacol 1979; 7: 624–7PubMedGoogle Scholar
  131. 131.
    White WB, Andreoli JW, Wong SH, et al. Atenolol in human plasma and breast milk. Obstet Gynecol 1984; 63: 42S–4SPubMedGoogle Scholar
  132. 132.
    Liedholm H, Melander A, Bitzen PO, et al. Accumulation of atenolol and metoprolol in human breast milk. Eur J Clin Pharmacol 1981; 20: 229–31PubMedGoogle Scholar
  133. 133.
    Lawton ME. Alcohol in breast milk. Aust NZ J Obstet Gynaecol 1985; 25: 71–3Google Scholar
  134. 134.
    Kesaniemi YA. Ethanol and acetaldehyde in the milk and peripheral blood of lactating women after ethanol administration. J Obstet Gynaecol Br Commonw 1974; 81: 84–6PubMedGoogle Scholar
  135. 135.
    Little RE, Anderson KW, Ervin CH, et al. Maternal alcohol use during breast feeding and infant mental and motor development at one year. N Engl J Med 1989; 321: 425–30PubMedGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • Ronen Loebstein
    • 1
  • Arieh Lalkin
    • 1
  • Gideon Koren
    • 1
  1. 1.Division of Clinical Pharmacology and ToxicologyThe Hospital for Sick ChildrenTorontoCanada

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