DRUG SAFETY IN BREASTFEEDING

 

Our department has had a long-term interest in the field of drug safety during breastfeeding, since we observed a deficiency of data through our Drug Information Service.  We have developed a widely used model for predicting drug concentrations in breast milk from the physicochemical properties of the drug (lipid solubility, plasma protein binding, pKa).  This model can be used to predict infant exposure when a clinical study is not available.  We have performed pharmacokinetic studies on the transfer of numerous drugs into breast milk including fluoxetine, paroxetine, methadone, metformin and olanzapine.  These studies allow us to make recommendations regarding the use of these agents in breastfeeding women.  We have also published a paper recommending best research practice for the study of drugs in human milk and have written one of the five leading chapters in the World Health Organization textbook in this field (see departmental publications).

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We are fortunate to collaborate with researchers from Western Australia (University of Western Australia, King Edward Memorial Hospital for Women and Western Australian Centre for Pathology and Medical Research) on the transfer of several drugs into breast milk including: paroxetine, fluoxetine, methadone, olanzapine and risperidone. For a look at their website try the following link: http://www.pharm.uwa.edu.au/drugs-milk/intro.html

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Refereed journal articles:

Gardiner SJ, Doogue MP, Zhang M, Begg EJ.  Quantification of infant exposure to celecoxib through breast milk. Br J Clin Pharmacol. 2006; 61(1): 101-4 [abstract]

 

Gardiner SJ , Gearry R B , Roberts RL , Zhang M, Barclay ML, Begg EJ.  Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharm. (online early version)

Gardiner SJ, Begg EJ. Breastfeeding during tacrolimus therapy. Obstetrics & Gynecology. 2006;107(2):453-455 [abstract]

Mei Zhang, Grant A. Moore, Sharon J. Gardiner, Evan J. Begg. Determination of celecoxib in human plasma and breast milk by high-performance liquid chromatographic assay.  Journal of Chromatography B.  2006; 830(2):245248 [abstract]

Ilett KF, Hackett LP, Kristensen JH, Vaddadi K, Gardiner SJ, Begg EJ. Transfer of risperidone and 9-hydroxyrisperidone into human milk: three case studies. Ann Pharmacother. 2004; 38(2): 273-6. [abstract]

 

Doogue MPD, Gardiner SJ, Begg EJ.  Predicting the breast milk to plasma concentration ratio of drugs.  Ann Pharmacother. 2004; 38(1): 172-177. [Letter]

Gardiner SJ, Kristensen JH, Begg EJ, Hackett LP, Wilson DA, Ilett KF, Kohan R, Rampono J.  Transfer of olanzapine into breast milk, calculation of infant drug dose, and effect on breast-fed infants.  Am J Psychiatry. 2003; 160(8):1428-31. [abstract]

Gardiner SJ, Kirkpatrick CMJ, Begg EJ, Zhang M, Moore MP, Saville DJ. Transfer of metformin into human milk. Clin Pharmacol Ther 2003; 73: 71-7. [link to abstract]

Begg EJ, Duffull SB, Hackett LP, Ilett KF. Studying drugs in human milk: time to improve the approach. J Hum Lact 2002; 18: 323-2. [link to abstract]

Begg EJ, Robson RA, Gardiner SJ, Hudson LJ, Reece PA, Olson SC, Posvar EL, Sedman AJ. Quinapril and its metabolite quinaprilat in human milk. Br J Clin Pharm 2001; 51: 478-81. [link to abstract]

Begg EJ, Malpas TJ, Hackett LP, Ilett KF. Distribution of R- and S-methadone into human milk at steady state during ingestion of medium to high doses. Br J Clin Pharm 2001; 52: 681-5. [link to abstract]

Zhang M, Moore GA, Lever M, Gardiner SJ, Kirkpatrick CMJ, Begg EJ. A rapid and simple HPLC assay for the determination of metformin in human plasma and breast milk. J Chromatogr B 2002; 766: 175-9. [link to abstract]

Begg EJ, Duffull SB, Saunders DA, Buttimore RC, Ilett KF, Hackett LP, Yapp P, Wilson DA. Paroxetine in human milk. Br J Clin Pharm 1999; 48: 142-7. [link to abstract]

Kristensen JH, Ilett LF, Hackett LP, Yapp P, Paech M, Begg EJ. Distribution and excretion of fluoxetine and norfluoxetine in human milk. Br J Clin Pharm 1999; 48: 521-7. [link to abstract]

Begg EJ, Atkinson HC. Modelling of the passage of drugs into milk. Pharmacol Ther 1993; 59: 301-10. [link to abstract]

Begg EJ, Atkinson HC, Duffull SB. Prospective evaluation of a model for the prediction of milk:plasma drug concentrations from physicochemical characteristics. Br J Clin Pharm 1992; 33: 501-6. [link to abstract]

Begg EJ, Atkinson HC. Partitioning of drugs into human milk. Ann Acad Med 1991; 20: 51-5. [link to abstract]

Atkinson HC, Begg EJ. Prediction of drug distribution into human milk from physicochemical characteristics. Clin Pharmacokinet 1990; 18: 151-67. [link to abstract]

Atkinson HC, Begg EJ. The binding of drugs to major human milk whey proteins. Br J Clin Pharm 1988; 26: 107-9. [link to abstract]

Atkinson HC, Begg EJ. Prediction of drug concentrations in human skim milk from plasma protein binding and acid-base characteristics. Br J Clin Pharm 1988; 25: 495-503. [link to abstract]

Atkinson HC, Begg EJ. Relationship between human milk lipid:ultrafiltrate and octanol-water partition coefficients. J Pharm Sci 1988; 77: 796-8. [link to abstract]

Atkinson HC, Begg EJ, Darlow BA. Drugs in human milk. Clinical pharmacokinetic considerations. Clin Pharmacokinet 1988; 14: 217-40. [link to abstract]

 

Book chapters:

Atkinson HC, Begg EJ. Drugs in human milk. In: Clinical pharmacokinetics drug data handbook (3rd edn). Holford NHG (ed), Auckland: ADIS Press, 1998 [ISBN 0312-5963] (1st Ed - 1989; 2nd ed - 1990).

Begg EJ. Determinants of drug transfer into human milk. In: Drugs and Human Lactation (2nd ed). Bennett PN (ed), Elsevier:Amsterdam, 1996 [ISBN 0 444 81981-9].

Begg EJ. Guide to drug usage during lactation. In: Avery's Drug Treatment (4th ed). Speight TM, Holford NHG (eds), Auckland:ADIS Press, 1997 [ISBN 0 86471 036 4].

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Page Last Updated: November 1 2006

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Clinical Pharmacology Department : Christchurch Hospital

private bag 4710 : christchurch : phone 0800 DRUGINFO (378 446) : email druginfo[AT]cdhb.govt.nz