Skip to main content
SpringerLink
Log in

Neonatal Exposure to Drugs in Breast Milk

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

There are many benefits of breast-feeding both for the infant and for the mother. Nursing mothers who are also taking medications or exposed to environmental hazards may be confronted with a difficult choice to discontinue nursing or maternal medication or risk potential harm to the infant. Frequently, these decisions are made without sufficient information or understanding of the factors influencing exposure. The current review explores two indices of exposure, together with their pharmacokinetic determinants. Both of the indices include the milk to serum (M/S) concentration ratio for a given drug and the volume of milk consumed. The first exposure term, EI(Dose), expresses neonatal dose as a percentage of maternal dose and is inversely related to the maternal systemic clearance. By contrast, the second exposure term, EI(Conc), expresses infant concentration as a percentage of maternal concentration and is inversely related to the infant systemic clearance. Issues related to intersubject variation in M/S (e.g., colostrum vs. mature milk, fore vs. hind milk) and infant clearance (e.g., ontogeny of elimination pathways, pharmacogenetics) and their role in modulating exposure are also discussed.

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

  1. A. L. Wright. The rise of breastfeeding in the United States. Pediatr. Clin. North Am. 48:1-12 (2001).

    Google Scholar 

  2. A. Wrightand and R. Schanler. The resurgence of breastfeeding at the end of the second millennium. J. Nutr. 131:421S-425S (2001).

    Google Scholar 

  3. H. Vorherr. The Breast, Academic Press, New York, 1974.

    Google Scholar 

  4. J. Wilson. Drugs in Breast Milk, ADIS Press, Auckland, 1981.

    Google Scholar 

  5. E. L. Mortensen, K. F. Michaelsen, S. A. Sanders, and J. M. Reinisch. The association between duration of breastfeeding and adult intelligence. JAMA 287:2365-2371 (2002).

    Google Scholar 

  6. Collaborative Group on Hormonal Factors in Breast Cancer Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 360:187-195 (2002).

    Google Scholar 

  7. S. L. Hatcher. The psychological experience of nursing mothers upon learning of a toxic substance in their breast milk. Psychiatry 45:172-181 (1982).

    Google Scholar 

  8. P. Bennet. Drugs and Human Lactation, Elsevier, Amsterdam, 1988.

    Google Scholar 

  9. P. O. Anderson. Drug use during breast-feeding. Clin. Pharm. 10:594-624 (1991).

    Google Scholar 

  10. S. Ito. Drug therapy for breast-feeding women. N. Engl. J. Med. 343:118-126 (2000).

    Google Scholar 

  11. C. M. BerlinJr. Drugs and chemicals: exposure of the nursing mother. Pediatr. Clin. North Am. 36:1089-1097 (1989).

    Google Scholar 

  12. S. A. Banta-Wright. Minimizing infant exposure to and risks from medications while breastfeeding. J. Perinat. Neonatal. Nurs. 11:71-84; quiz 85–86 (1997).

    Google Scholar 

  13. H. C. Atkinson, E. J. Begg, and B. A. Darlow. Drugs in human milk. Clinical pharmacokinetic considerations. Clin. Pharmacokinet. 14:217-240 (1988).

    Google Scholar 

  14. J. T. Wilson, R. D. Brown, D. R. Cherek, J. W. Dailey, B. Hilman, P. C. Jobe, B. R. Manno, J. E. Manno, H. M. Redetzki, and J. J. Stewart. Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences. Clin. Pharmacokinet. 5:1-66 (1980).

    Google Scholar 

  15. J. T. Wilson. Determinants and consequences of drug excretion in breast milk. Drug Metab. Rev. 14:619-652 (1983).

    Google Scholar 

  16. J. T. Wilson, R. D. Brown, J. L. Hinson, and J. W. Dailey. Pharmacokinetic pitfalls in the estimation of the breast milk/plasma ratio for drugs. Annu. Rev. Pharmacol. Toxicol. 25:667-689 (1985).

    Google Scholar 

  17. C. M. Berlin. The excretion of drugs in human milk. Prog. Clin. Biol. Res. 36:115-127 (1980).

    Google Scholar 

  18. C. M. BerlinJr. Pharmacologic considerations of drug use in thelactating mother. Obstet. Gynecol. 58:17S-23S (1981).

    Google Scholar 

  19. J. C. Fleishaker, N. Desai, and P. J. McNamara. Factors affecting the milk-to-plasma drug concentration ratio in lactating women: physical interactions with protein and fat. J. Pharm. Sci. 76:189-193 (1987).

    Google Scholar 

  20. H. C. Atkinson and E. J. Begg. Prediction of drug distribution into human milk from physicochemical characteristics. Clin. Pharmacokinet. 18:151-167 (1990).

    Google Scholar 

  21. S. Ito and A. Lee. Drug excretion into breast milk—overview. Adv. Drug Deliv. Rev. 55:617-627 (2003).

    Google Scholar 

  22. J. C. Fleishaker. Models and methods for predicting drug transfer into human milk. Adv. Drug Deliv. Rev. 55:643-652 (2003).

    Google Scholar 

  23. K. Yoshida, B. Smith, M. Craggs, and R. C. Kumar. Fluoxetine in breast-milk and developmental outcome of breast-fed infants. Br. J. Psychiatry 172:175-178 (1998).

    Google Scholar 

  24. V. Hendrick, A. Fukuchi, L. Altshuler, M. Widawski, A. Wertheimer, and M. V. Brunhuber. Use of sertraline, paroxetine and fluvoxamine by nursing women. Br. J. Psychiatry 179:163-166 (2001).

    Google Scholar 

  25. V. Hendrick, Z. N. Stowe, L. L. Altshuler, J. Mintz, S. Hwang, A. Hostetter, R. Suri, K. Leight, and A. Fukuchi. Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk. Biol. Psychiatry 50:775-782 (2001).

    Google Scholar 

  26. N. Epperson, K. A. Czarkowski, D. Ward-O'Brien, E. Weiss, R. Gueorguieva, P. Jatlow, and G. M. Anderson. Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs. Am. J. Psychiatry 158:1631-1637 (2001).

    Google Scholar 

  27. C. M. Berlin. Sensitivity of the young infant to drug exposure through human milk. Adv. Drug Deliv. Rev. 55:687-693 (2003).

    Google Scholar 

  28. S. Ito and G. Koren. A novel index for expressing exposure of the infant to drugs in breast milk. Br. J. Clin. Pharmacol. 38:99-102 (1994).

    Google Scholar 

  29. M. C. Neville and C. T. Walsh. Effects of xenobiotics on milk secretion and composition. Am. J. Clin. Nutr. 61:687S-694S (1995).

    Google Scholar 

  30. J. L. Dorne, K. Walton, and A. G. Renwick. Uncertainty factors for chemical risk assessment. Human variability in the pharmacokinetics of CYP1A2 probe substrates. Food Chem. Toxicol. 39:681-696 (2001).

    Google Scholar 

  31. J. L. Brazier, J. Ritter, M. Berland, D. Khenfer, and G. Faucon. Pharmacokinetics of caffeine during and after pregnancy. Dev. Pharmacol. Ther. 6:315-322 (1983).

    Google Scholar 

  32. J. V. Aranda, J. M. Collinge, R. Zinman, and G. Watters. Maturation of caffeine elimination in infancy. Arch. Dis. Child. 54:946-949 (1979).

    Google Scholar 

  33. C. Y. Oo, D. E. Burgio, R. C. Kuhn, N. Desai, and P. J. McNamara. Pharmacokinetics of caffeine and its demethylated metabolites in lactation: predictions of milk to serum concentration ratios. Pharm. Res. 12:313-316 (1995).

    Google Scholar 

  34. M. C. Neville and J. Morton. Physiology and endocrine changes underlying human lactogenesis II. J. Nutr. 131:3005S-3008S (2001).

    Google Scholar 

  35. G. M. Chan. Lactation: the Breast-Feeding Manual for Health Professionals, Precept, Chicago, 1997.

    Google Scholar 

  36. L. Borgatta, R. W. Jenny, L. Gruss, C. Ong, and D. Barad. Clinical significance of methohexital, meperidine, and diazepam in breast milk. J. Clin. Pharmacol. 37:186-192 (1997).

    Google Scholar 

  37. V. L. Feilberg, D. Rosenborg, C. Broen Christensen, and J. V. Mogensen. Excretion of morphine in human breast milk. Acta Anaesthesiol. Scand. 33:426-428 (1989).

    Google Scholar 

  38. N. E. Baka, F. Bayoumeu, M. J. Boutroy, and M. C. Laxenaire. Colostrum morphine concentrations during postcesarean intravenous patient-controlled analgesia. Anesth. Analg. 94:184-187 (2002).

    Google Scholar 

  39. Z. Esener, B. Sarihasan, H. Guven, and E. Ustun. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. Br. J. Anaesth. 69:586-588 (1992).

    Google Scholar 

  40. L. W. Andersen, T. Qvist, J. Hertz, and F. Mogensen. Concentrations of thiopentone in mature breast milk and colostrum following an induction dose. Acta Anaesthesiol. Scand. 31:30-32 (1987).

    Google Scholar 

  41. K. Yoshida, B. Smith, M. Craggs, and R. C. Kumar. Investigation of pharmacokinetics and of possible adverse effects in infants exposed to tricyclic antidepressants in breast-milk. J. Affect. Disord. 43:225-237 (1997).

    Google Scholar 

  42. Z. N. Stowe, L. S. Cohen, A. Hostetter, J. C. Ritchie, M. J. Owens, and C. B. Nemeroff. Paroxetine in human breast milk and nursing infants. Am. J. Psychiatry 157:185-189 (2000).

    Google Scholar 

  43. Z. N. Stowe, M. J. Owens, J. C. Landry, C. D. Kilts, T. Ely, A. Llewellyn, and C. B. Nemeroff. Sertraline and desmethylsertraline in human breast milk and nursing infants. Am. J. Psychiatry 154:1255-1260 (1997).

    Google Scholar 

  44. M. F. Goldfarb and M. S. Savadove. Creamatocrit and pH measurements of human milk. J. Pediatr. Gastroenterol. Nutr. 12:142-143 (1991).

    Google Scholar 

  45. J. H. Kristensen, K. F. Ilett, L. P. Hackett, P. Yapp, M. Paech, and E. J. Begg. Distribution and excretion of fluoxetine and norfluoxetine in human milk. Br. J. Clin. Pharmacol. 48:521-527 (1999).

    Google Scholar 

  46. J. H. Kristensen, K. F. Ilett, L. J. Dusci, L. P. Hackett, P. Yapp, R. E. Wojnar-Horton, M. J. Roberts, and M. Paech. Distribution and excretion of sertraline and N-desmethylsertraline in human milk. Br. J. Clin. Pharmacol. 45:453-457 (1998).

    Google Scholar 

  47. J. Rampono, J. H. Kristensen, L. P. Hackett, M. Paech, R. Kohan, and K. F. Ilett. Citalopram and demethylcitalopram in human milk; distribution, excretion and effects in breast fed infants. Br. J. Clin. Pharmacol. 50:263-268 (2000).

    Google Scholar 

  48. S. Kaneko, T. Sato, and K. Suzuki. The levels of anticonvulsants in breast milk. Br. J. Clin. Pharmacol. 7:624-627 (1979).

    Google Scholar 

  49. W. Kuhnz, S. Koch, H. Helge, and H. Nau. Primidone and phenobarbital during lactation period in epileptic women: total and free drug serum levels in the nursed infants and their effects on neonatal behavior. Dev. Pharmacol. Ther. 11:147-154 (1988).

    Google Scholar 

  50. W. Froescher, M. Eichelbaum, M. Niesen, K. Dietrich, and P. Rausch. Carbamazepine levels in breast milk. Ther. Drug Monit. 6:266-271 (1984).

    Google Scholar 

  51. J. Alcorn, X. Lu, J. A. Moscow, and P. J. McNamara. Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction. J. Pharmacol. Exp. Ther. 303:487-496 (2002).

    Google Scholar 

  52. S. Ito and J. Alcorn. Xenobiotic transporter expression and function in the human mammary gland. Adv. Drug Deliv. Rev. 55:653-665 (2003).

    Google Scholar 

  53. C. Y. Oo, R. J. Kuhn, N. Desai, and P. J. McNamara. Active transport of cimetidine into human milk. Clin. Pharmacol. Ther. 58:548-555 (1995).

    Google Scholar 

  54. P. M. Gerk, R. J. Kuhn, N. S. Desai, and P. J. McNamara. Active transport of nitrofurantoin into human milk. Pharmacotherapy 21:669-675 (2001).

    Google Scholar 

  55. J. Alcorn and P. J. McNamara. the ontogeny of hepatic and renal systemic clearance pathways in infants: a review (part I). Clin. Pharmacokinet. 41:959-998 (2002).

    Google Scholar 

  56. J. Alcorn and P. J. McNamara. The ontogeny of hepatic and renal systemic clearance pathways in infants: model predictions (part II). Clin. Pharmacokinet. 41:1077-1094 (2002).

    Google Scholar 

  57. J. Alcorn and P. J. McNamara. Pharmacokinetics in the newborn. Adv. Drug Deliv. Rev. 55:667-686 (2003).

    Google Scholar 

  58. T. Cresteil. Onset of xenobiotic metabolism in children: toxicological implications. Food Addit. Contam. 15:45-51 (1998).

    Google Scholar 

  59. S. Caccia. Metabolism of the newer antidepressants. An overview of the pharmacological and pharmacokinetic implications. Clin. Pharmacokinet. 34:281-302 (1998).

    Google Scholar 

  60. C. Hiemke and S. Hartter. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol. Ther. 85:11-28 (2000).

    Google Scholar 

  61. H. L. McLeod and W. E. Evans. Pharmacogenomics: unlocking the human genome for better drug therapy. Annu. Rev. Pharmacol. Toxicol. 41:101-121 (2001).

    Google Scholar 

  62. O. Spigset and S. Hagg. Excretion of psychotropic drugs into breast milk; pharmacokinetic overview and therapeutic implications. CNS Drugs 9:111-134 (1998).

    Google Scholar 

  63. L. Bertilsson, M. L. Dahl, P. Dalen, and A. Al-Shurbaji. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br. J. Clin. Pharmacol. 53:111-122 (2002).

    Google Scholar 

  64. J. H. Kristensen, L. P. Hackett, R. Kohan, M. Paech, and K. F. Ilett. The amount of fluvoxamine in milk is unlikely to be a cause of adverse effects in breastfed infants. J. Hum. Lact. 18:139-143 (2002).

    Google Scholar 

  65. E. J. Begg, S. B. Duffull, D. A. Saunders, R. C. Buttimore, K. F. Ilett, L. P. Hackett, P. Yapp, and D. A. Wilson. Paroxetine in human milk. Br. J. Clin. Pharmacol. 48:142-147 (1999).

    Google Scholar 

  66. K. F. Ilett, L. P. Hackett, L. J. Dusci, M. J. Roberts, J. H. Kristensen, M. Paech, A. Groves, and P. Yapp. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br. J. Clin. Pharmacol. 45:459-462 (1998).

    Google Scholar 

  67. N. Poolsup, A. Li Wan Po, and T. L. Knight. Pharmacogenetics and psychopharmacotherapy. J. Clin. Pharm. Ther. 25:197-220 (2000).

    Google Scholar 

  68. C. R. Howard and R. A. Lawrence. Drugs and breastfeeding. Clin. Perinatol. 26:447-478 (1999).

    Google Scholar 

  69. M. J. Boutroy, G. Bianchetti, C. Dubruc, P. Vert, and P. L. Morselli. To nurse when receiving acebutolol: is it dangerous for the neonate? Eur. J. Clin. Pharmacol. 30:737-739 (1986).

    Google Scholar 

  70. G. Bianchetti, C. Dubroc, P. Vert, M. Boutroy, and P. Morselli. Placental transfer and pharmacokinetics of acebutolol in newborn infants. Clin. Pharmacol. Ther. 29:233-234 (1981).

    Google Scholar 

  71. B. N. Singh, W. R. Thoden, and J. Wahl. Acebutolol: a review of its pharmacology, pharmacokinetics, clinical uses, and adverse effects. Pharmacotherapy 6:45-63 (1986).

    Google Scholar 

  72. B. J. Anderson, N. H. Holford, G. A. Woollard, and P. L. Chan. Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children. Br. J. Clin. Pharmacol. 46:237-243 (1998).

    Google Scholar 

  73. W. Kuhnz, E. Jager-Roman, D. Rating, A. Deichl, J. Kunze, H. Helge, and H. Nau. Carbamazepine and carbamazepine-10,11-epoxide during pregnancy and postnatal period in epileptic mother and their nursed infants: pharmacokinetics and clinical effects. Pediatr Pharmacol 3:199-208 (1983).

    Google Scholar 

  74. S. Pynnonen, J. Kanto, M. Sillanpaa, and R. Erkkola. Carbamazepine: placental transport, tissue concentrations in foetus and newborn, and level in milk. Acta Pharmacol. Toxicol. (Copenh.) 41:244-253 (1977).

    Google Scholar 

  75. L. Bertilsson and T. Tomson. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide. An update. Clin. Pharmacokinet. 11:177-198 (1986).

    Google Scholar 

  76. E. Rey, P. d'Athis, D. de Lauture, O. Dulac, J. Aicardi, and G. Olive. Pharmacokinetics of carbamazepine in the neonate and in the child. Int. J. Clin. Pharmacol. Biopharm. 17:90-96 (1979).

    Google Scholar 

  77. J. Knowles. Drugs in milk. Pediatr. Currents 21:28-32 (1972).

    Google Scholar 

  78. P. Periti, T. Mazzei, E. Mini, and A. Novelli. Clinical pharmacokinetic properties of the macrolide antibiotics. Effects of age and various pathophysiological states (part II). Clin. Pharmacokinet. 16:261-282 (1989).

    Google Scholar 

  79. K. B. Waites, P. J. Sims, D. T. Crouse, M. H. Geerts, R. E. Shoup, W. B. Hamrick, L. B. Duffy, and G. H. Cassell. Serum concentrations of erythromycin after intravenous infusion in preterm neonates treated for ureaplasma urealyticum infection. Pediatr. Infect. Dis. J. 13:287-293 (1994).

    Google Scholar 

  80. X. Wagner, J. Jouglard, M. Moulin, A. M. Miller, J. Petitjean, and A. Pisapia. Coadministration of flecainide acetate and sotalol during pregnancy: lack of teratogenic effects, passage across the placenta, and excretion in human breast milk. Am. Heart J. 119:700-702 (1990).

    Google Scholar 

  81. R. L. McQuinn, A. Pisani, S. Wafa, S. F. Chang, A. M. Miller, J. M. Frappell, G. V. Chamberlain, and A. J. Camm. Flecainide excretion in human breast milk. Clin. Pharmacol. Ther. 48:262-267 (1990).

    Google Scholar 

  82. C. Funck-Brentano, L. Becquemont, H. K. Kroemer, K. Buhl, N. G. Knebel, M. Eichelbaum, and P. Jaillon. Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clin. Pharmacol. Ther. 55:256-269 (1994).

    Google Scholar 

  83. J. A. Till, E. A. Shinebourne, E. Rowland, D. E. Ward, R. Bhamra, P. Haga, A. Johnston, and D. W. Holt. Paediatric use of flecainide in supraventricular tachycardia: clinical efficacy and pharmacokinetics. Br. Heart J. 62:133-139 (1989).

    Google Scholar 

  84. T. H. Lebedevs, R. E. Wojnar-Horton, P. Yapp, M. J. Roberts, L. J. Dusci, L. P. Hackett, and K. F. Ilett. Excretion of indomethacin in breast milk. Br. J. Clin. Pharmacol. 32:751-754 (1991).

    Google Scholar 

  85. O. Eeg-Olofsson, I. Malmros, C. E. Elwin, and B. Steen. Convulsions in a breast-fed infant after maternal indomethacin. Lancet 2:215(1978).

    Google Scholar 

  86. R. Oberbauer, P. Krivanek, and K. Turnheim. Pharmacokinetics of indomethacin in the elderly. Clin. Pharmacokinet. 24:428-434 (1993).

    Google Scholar 

  87. M. Weninger, A. Pollak, U. Salzer-Muhar, K. A. Vergesslich, and H. R. Salzer. Pharmacokinetics of intra-arterial indomethacin treatment for patent ductus arteriosus. Eur. J. Pediatr. 149:138-140 (1989).

    Google Scholar 

  88. G. Briggs, R. Freeman, and S. Yaffe. Drugs in Pregnancy and Lactation, Williams & Wilkins, Baltimore, 1998.

    Google Scholar 

  89. J. Heykants, M. Michiels, W. Meuldermans, J. Monbaliu, K. Lavrijsen, A. Van Peer, J. Levran, R. Woestenbourghs, and G. Cauwenbergh. The pharmacokinetics or itraconazole in animals and man. An overview. In R. Fromtling (ed.), Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents, Prous Science Publisher, Barcelona, 1987.

    Google Scholar 

  90. L. de Repentigny, J. Ratelle, J. M. Leclerc, G. Cornu, E. M. Sokal, P. Jacqmin, and K. De Beule. Repeated-dose pharmacokinetics of an oral solution of itraconazole in infants and children. Antimicrob. Agents Chemother. 42:404-408 (1998).

    Google Scholar 

  91. A. G. Whitelaw, A. J. Cummings, and I. R. McFadyen. Effect of maternal lorazepam on the neonate. Br. Med. J. (Clin. Res. Ed.) 282:1106-8 (1981).

    Google Scholar 

  92. R. J. Summerfield and M. S. Nielsen. Excretion of lorazepam into breast milk. Br. J. Anaesth. 57:1042-1043 (1985).

    Google Scholar 

  93. D. J. Greenblatt. Clinical pharmacokinetics of oxazepam and lorazepam. Clin. Pharmacokinet. 6:89-105 (1981).

    Google Scholar 

  94. W. R. Crom, M. V. Relling, M. L. Christensen, G. K. Rivera, and W. E. Evans. Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. Clin. Pharmacol. Ther. 50:132-140 (1991).

    Google Scholar 

  95. C. A. McDermott, A. L. Kowalczyk, E. R. Schnitzler, H. H. Mangurten, K. A. Rodvold, and S. Metrick. Pharmacokinetics of lorazepamin critically ill neonates with seizures. J. Pediatr. 120:479-483 (1992).

    Google Scholar 

  96. A. Kauppila, P. Arvela, M. Koivisto, S. Kivinen, O. Ylikorkala, and O. Pelkonen. Metoclopramide and breast feeding: transfer into milk and the newborn. Eur. J. Clin. Pharmacol. 25:819-823 (1983).

    Google Scholar 

  97. K. Lauritsen, L. S. Laursen, and J. Rask-Madsen. Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II). Clin. Pharmacokinet. 19:94-125 (1990).

    Google Scholar 

  98. G. L. Kearns, J. N. van den Anker, M. D. Reed, and J. L. Blumer. Pharmacokinetics of metoclopramide in neonates. J. Clin. Pharmacol. 38:122-128 (1998).

    Google Scholar 

  99. G. L. Kearns, H. L. Butler, J. K. Lane, S. H. Carchman, and G. J. Wright. Metoclopramide pharmacokinetics and pharmacodynamics in infants with gastroesophageal reflux. J. Pediatr. Gastroenterol. Nutr. 7:823-829 (1988).

    Google Scholar 

  100. I. Matheson, P. K. Lunde, and J. E. Bredesen. Midazolam and nitrazepam in the maternity ward: milk concentrations and clinical effects. Br. J. Clin. Pharmacol. 30:787-793 (1990).

    Google Scholar 

  101. P. D. Garzone and P. D. Kroboth. Pharmacokinetics of the newer benzodiazepines. Clin. Pharmacokinet. 16:337-364 (1989).

    Google Scholar 

  102. T. C. Lee, B. G. Charles, G. J. Harte, P. H. Gray, P. A. Steer, and V. J. Flenady. Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics. Anesthesiology 90:451-457 (1999).

    Google Scholar 

  103. P. Burtin, E. Jacqz-Aigrain, P. Girard, R. Lenclen, J. F. Magny, P. Betremieux, C. Tehiry, L. Desplanques, and P. Mussat. Population pharmacokinetics of midazolam neonates. Clin. Pharmacol. Ther. 56:615-625 (1994).

    Google Scholar 

  104. J. K. Marshall, A. B. Thompson, and D. Armstrong. Omeprazole for refractory gastroesophageal reflux disease during pregnancy and lactation. Can. J. Gastroenterol. 12:225-227 (1998).

    Google Scholar 

  105. M. Chang, G. Tybring, M. L. Dahl, E. Gotharson, M. Sagar, R. Seensalu, and L. Bertilsson. Interphenotype differences in disposition and effect on gastrin levels of omeprazole—suitability of omeprazole as a probe for CYP2C19. Br. J. Clin. Pharmacol. 39:511-518 (1995).

    Google Scholar 

  106. E. Jacqz-Aigrain, M. Bellaich, C. Faure, J. Andre, P. Rohrlich, V. Baudouin, and J. Navarro. Pharmacokinetics of intravenous omeprazole in children. Eur. J. Clin. Pharmacol. 47:181-185 (1994).

    Google Scholar 

  107. A. M. Yurchak and W. J. Jusko. Theophylline secretion into breast milk. Pediatrics 57:518-520 (1976).

    Google Scholar 

  108. G. P. Stec, P. Greenberger, T. I. Ruo, T. Henthorn, Y. Morita, A. J. AtkinsonJr., and R. Patterson. Kinetics of theophylline transfer to breast milk. Clin. Pharmacol. Ther. 28:404-408 (1980).

    Google Scholar 

  109. A. M. Taburet and B. Schmit. Pharmacokinetic optimisation of asthma treatment. Clin. Pharmacokinet. 26:396-418 (1994).

    Google Scholar 

  110. J. V. Aranda, D. S. Sitar, W. D. Parsons, P. M. Loughnan, and A. H. Neims. Pharmacokinetic aspects of theophylline in premature newborns. N. Engl. J. Med. 295:413-416 (1976).

    Google Scholar 

  111. J. T. Gilman, P. Gal, R. S. Levine, C. B. Hersh, and N. V. Erkan. Factors influencing theophylline disposition in 179 newborns. Ther. Drug Monit. 8:4-10 (1986).

    Google Scholar 

  112. H. W. Ahn, W. G. Shin, K. J. Park, O. K. Suh, and J. H. Choi. Pharmacokinetics of theophylline and caffeine after intravenous administration of aminophylline to premature neonates in Korea. Res. Commun. Mol. Pathol. Pharmacol. 105:105-113 (1999).

    Google Scholar 

  113. E. S. Moore, R. G. Faix, R. C. Banagale, and T. H. Grasela. The population pharmacokinetics of theophylline in neonates and young infants. J. Pharmacokinet. Biopharm. 17:47-66 (1989).

    Google Scholar 

  114. D. M. Hilligoss, W. J. Jusko, J. R. Koup, and G. Giacoia. Factors affecting theophylline pharmacokinetics in premature infants with apnea. Dev. Pharmacol. Ther. 1:6-15 (1980).

    Google Scholar 

  115. H. Nau, D. Rating, S. Koch, I. Hauser, and H. Helge. Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers. J. Pharmacol. Exp. Ther. 219:768-777 (1981).

    Google Scholar 

  116. N. Tsuru, T. Maeda, and M. Tsuruoka. Three cases of delivery under sodium valproate—placental transfer, milk transfer and probable teratogenicity of sodium valproate. Jpn. J. Psychiatry Neurol. 42:89-96 (1988).

    Google Scholar 

  117. A. Philbert, B. Pedersen, and M. Dam. Concentration of valproate during pregnancy, in the newborn and in breast milk. Acta Neurol. Scand. 72:460-463 (1985).

    Google Scholar 

  118. G. Zaccara, A. Messori, and F. Moroni. Clinical pharmacokinetics of valproic acid—1988. Clin. Pharmacokinet. 15:367-389 (1988).

    Google Scholar 

  119. D. Battino, M. Estienne, and G. Avanzini. Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I: phenobarbital, primidone, valproic acid, ethosuximide and mesuximide. Clin. Pharmacokinet. 29:257-286 (1995).

    Google Scholar 

  120. L. Herngren, B. Lundberg, and A. Nergardh. Pharmacokinetics of total and free valproic acid during monotherapy in infants. J. Neurol. 238:315-319 (1991).

    Google Scholar 

  121. G. D. Morse, M. J. Shelton, and A. M. O'Donnell. Comparative pharmacokinetics of antiviral nucleoside analogues. Clin. Pharmacokinet. 24:101-123 (1993).

    Google Scholar 

  122. M. Mirochnick, E. Capparelli, and J. Connor. Pharmacokinetics of zidovudine in infants: a population analysis across studies. Clin. Pharmacol. Ther. 66:16-24 (1999).

    Google Scholar 

  123. M. Mirochnick, E. Capparelli, W. Dankner, R. S. Sperling, R. van Dyke, and S. A. Spector. Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus. Antimicrob. Agents Chemother. 42:808-812 (1998).

    Google Scholar 

  124. F. D. Boucher, J. F. Modlin, S. Weller, A. Ruff, M. Mirochnick, S. Pelton, C. Wilfert, R. McKinneyJr., M. J. Crain, M. M. Elkins, et al. Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus. J. Pediatr. 122:137-144 (1993).

    Google Scholar 

  125. J. M. Hopkinson, R. J. Schanler, J. K. Fraley, and C. Garza. Milk production by mothers of premature infants: influence of cigarette smoking. Pediatrics 90:934-938 (1992).

    Google Scholar 

  126. K. E. Thummel and D. Shen. Appendix II, design and optimization of dosage regimens; pharmacokinetic data. In L. Goodman, L. Limbird, P. Milinoff, A. Gilman, and J. Hardman (eds), The Pharmacological Basis of Therapeutics, McGraw-Hill, New York, 2001, pp. 1917-2024.

    Google Scholar 

  127. P. N. Jensen, O. V. Olesen, A. Bertelsen, and K. Linnet. Citalopram and desmethylcitalopram concentrations in breast milk and in serum of mother and infant. Ther. Drug Monit. 19:236-239 (1997).

    Google Scholar 

  128. O. Spigset, L. Carieborg, R. Ohman, and A. Norstrom. Excretion of citalopram in breast milk. Br. J. Clin. Pharmacol. 44:295-298 (1997).

    Google Scholar 

  129. K. E. Isenberg. Excretion of fluoxetine in human breast milk. J. Clin. Psychiatry 51:169(1990).

    Google Scholar 

  130. S. Wright, S. Dawling, and J. J. Ashford. Excretion of fluvoxamine in breast milk. Br. J. Clin. Pharmacol. 31:209(1991).

    Google Scholar 

  131. O. Spigset, L. Carleborg, A. Norstrom, and M. Sandlund. Paroxetine level in breast milk. J. Clin. Psychiatry 57:39(1996).

    Google Scholar 

  132. R. Ohman, S. Hagg, L. Carleborg, and O. Spigset. Excretion of paroxetine into breast milk. J. Clin. Psychiatry 60:519-523 (1999).

    Google Scholar 

  133. L. L. Altshuler, V. K. Burt, M. McMullen, and V. Hendrick. Breastfeeding and sertraline: a 24-hour analysis. J. Clin. Psychiatry 56:243-245 (1995).

    Google Scholar 

  134. K. F. Ilett, J. H. Kristensen, L. P. Hackett, M. Paech, R. Kohan. and J. Rampono. Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br. J. Clin. Pharmacol. 53:17-22 (2002).

    Google Scholar 

  135. S. Rattigan, A. V. Ghisalberti, and P. E. Hartmann. Breast-milk production in Australian women. Br. J. Nutr. 45:243-249 (1981).

    Google Scholar 

  136. N. F. Butte, C. Garza, J. E. Stuff, E. O. Smith, and B. L. Nichols. Effect of maternal diet and body composition on lactational performance. Am. J. Clin. Nutr. 39:296-306 (1984).

    Google Scholar 

  137. M. C. Neville. Physiology of lactation. Clin. Perinatol. 26:251-279 (1999).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, University of Kentucky, Lexington, Kentucky, 40536

    Patrick J. McNamara & Maggie Abbassi

Authors
  1. Patrick J. McNamara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maggie Abbassi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick J. McNamara.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McNamara, P.J., Abbassi, M. Neonatal Exposure to Drugs in Breast Milk. Pharm Res 21, 555–566 (2004). https://doi.org/10.1023/B:PHAM.0000022401.14710.c5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:PHAM.0000022401.14710.c5

Search

Navigation