母乳育児と母親の薬について

新生児における薬物動態に影響する諸因子とその成人レベルに達する時期の目安

乳児への薬剤曝露量決定要因は、薬剤の母乳移行性や母乳摂取量のみならず、乳児の薬剤消化管吸収、薬剤処理能力（肝機能、腎機能など）が大きく関わる。

肝代謝酵素の発達経過

薬剤処理能力に関わる肝薬物代謝酵素の発達変化は酵素の種類により異なるため、同じ薬剤であっても月齢・年齢により、また同じ年齢でも使用する薬剤により受ける影響が異なる可能性がある。
 
参考文献：
1. 越前宏俊監修：今日の治療指針2017年度版. 医学書院, 2017
2. Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children. Clin Pharmacokinet. 2006;45(9):931-56. PMID: 16928154
3. Maples, HD, et al. Chapter 10, Special pharmacokinetic and Pharmacodynamic Considerations in Children. In: Burton ME, Shaw LM, Schentag JJ, Evans WE eds. Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring 4th edtion. Lippincott Williams & Wilkins, Philadelphia, PA, 2005
4. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med, 2003. 349 (12): 1157-67. PMID: 13679531
5. Sin Yin Lim, Rebecca S Pettit：Pharmacokinetic considerations in pediatric pharmacotherapy. Am J Health Syst Pharm. 2019 Sep 16;76(19):1472-1480. PMID：31532503
6. M J Blake, A Gaedigk, R E Pearce, L R Bomgaars, et al.：Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther. 2007 Apr;81(4):510-6. PMID：17301735
7. Shogo J Miyagi, Abby C Collier：Pediatric development of glucuronidation: the ontogeny of hepatic UGT1A4. Drug Metab Dispos. 2007 Sep;35(9):1587-92. PMID：17556526
出典
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1: 著者提供

各薬剤のM/P比、pKaおよびタンパク結合率

母親の血中薬物曝露量（AUC）と乳汁中薬物曝露量（AUC）の比を乳汁／血漿薬物濃度比（milk-to-plasma drug concentration ratio、M/P比）といい、薬剤の母乳への移行性を示す指標として使用される。
出典
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1: Prediction of milk/plasma concentration ratio of drugs.
著者: Line Alleslev Larsen, Shinya Ito, Gideon Koren
雑誌名: Ann Pharmacother. 2003 Sep;37(9):1299-306. doi: 10.1345/aph.1C379.
Abstract/Text: OBJECTIVE: The milk to plasma (m/p) concentration ratio of drugs is used to estimate the amount of drug offered to the suckling infant. Published literature was reviewed to identify drugs for which sufficient data exist for calculation of m/p ratio and to examine whether the existing empiric data agree with the published method of Atkinson for mathematical prediction of m/p ratios based on physiochemical characteristics.
METHODS: Using a comprehensive reference text, we identified studies reporting sufficient data to calculate m/p ratio based on the AUC for milk and plasma. Subsequently, we calculated the m/p ratio with Atkinson's formula based on pKa, lipophilicity, and protein binding. We then correlated the empiric versus predicted (calculated) m/p ratios.
RESULTS: Of 192 drugs of which at least some data on milk accumulation have been published, there were sufficient data to quantify m/p ratios for only 69 medications (78 studies). There was no significant correlation between the empiric m/p ratios and the predicted values using the Atkinson's model.
CONCLUSIONS: Reliable data on m/p concentration ratios exist for few medications. Presently, there is no appropriate model to predict milk concentrations of drugs in humans.
Ann Pharmacother. 2003 Sep;37(9):1299-306. doi: 10.1345/aph.1C379.

乳児の母乳中薬剤曝露レベル（Exposure Index: EI）とM/P比および薬剤クリアランスの関係

母乳を介した乳児の薬剤曝露レベルは移行性（M/P比）だけでは決定されない。M/P比が高い薬剤であっても患児の薬剤クリアランスの上昇に伴い曝露量は低下する。 EIが10％未満であれば臨床的には問題ないとされていることから、薬剤クリアランスが重要である。
出典
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1: Drug therapy for breast-feeding women.
N Engl J Med. 2000 Jul 13;343(2):118-26. doi: 10.1056/NEJM200007133430208.

放射性医薬品の授乳中止期間

放射性医薬品を使用する際の授乳中止期間は、放射線の減衰速度に基づいて算出される。
出典
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1: The transfer of drugs and therapeutics into human breast milk: an update on selected topics.
著者: Hari Cheryl Sachs, Committee On Drugs
雑誌名: Pediatrics. 2013 Sep;132(3):e796-809. doi: 10.1542/peds.2013-1985. Epub 2013 Aug 26.
Abstract/Text: Many mothers are inappropriately advised to discontinue breastfeeding or avoid taking essential medications because of fears of adverse effects on their infants. This cautious approach may be unnecessary in many cases, because only a small proportion of medications are contraindicated in breastfeeding mothers or associated with adverse effects on their infants. Information to inform physicians about the extent of excretion for a particular drug into human milk is needed but may not be available. Previous statements on this topic from the American Academy of Pediatrics provided physicians with data concerning the known excretion of specific medications into breast milk. More current and comprehensive information is now available on the Internet, as well as an application for mobile devices, at LactMed (http://toxnet.nlm.nih.gov). Therefore, with the exception of radioactive compounds requiring temporary cessation of breastfeeding, the reader will be referred to LactMed to obtain the most current data on an individual medication. This report discusses several topics of interest surrounding lactation, such as the use of psychotropic therapies, drugs to treat substance abuse, narcotics, galactagogues, and herbal products, as well as immunization of breastfeeding women. A discussion regarding the global implications of maternal medications and lactation in the developing world is beyond the scope of this report. The World Health Organization offers several programs and resources that address the importance of breastfeeding (see http://www.who.int/topics/breastfeeding/en/).
Pediatrics. 2013 Sep;132(3):e796-809. doi: 10.1542/peds.2013-1985. Epu...

用量依存性を認める母乳の利点

出典
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1: Breastfeeding and the use of human milk.
著者: Section on Breastfeeding
雑誌名: Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub 2012 Feb 27.
Abstract/Text: Breastfeeding and human milk are the normative standards for infant feeding and nutrition. Given the documented short- and long-term medical and neurodevelopmental advantages of breastfeeding, infant nutrition should be considered a public health issue and not only a lifestyle choice. The American Academy of Pediatrics reaffirms its recommendation of exclusive breastfeeding for about 6 months, followed by continued breastfeeding as complementary foods are introduced, with continuation of breastfeeding for 1 year or longer as mutually desired by mother and infant. Medical contraindications to breastfeeding are rare. Infant growth should be monitored with the World Health Organization (WHO) Growth Curve Standards to avoid mislabeling infants as underweight or failing to thrive. Hospital routines to encourage and support the initiation and sustaining of exclusive breastfeeding should be based on the American Academy of Pediatrics-endorsed WHO/UNICEF "Ten Steps to Successful Breastfeeding." National strategies supported by the US Surgeon General's Call to Action, the Centers for Disease Control and Prevention, and The Joint Commission are involved to facilitate breastfeeding practices in US hospitals and communities. Pediatricians play a critical role in their practices and communities as advocates of breastfeeding and thus should be knowledgeable about the health risks of not breastfeeding, the economic benefits to society of breastfeeding, and the techniques for managing and supporting the breastfeeding dyad. The "Business Case for Breastfeeding" details how mothers can maintain lactation in the workplace and the benefits to employers who facilitate this practice.
Pediatrics. 2012 Mar;129(3):e827-41. doi: 10.1542/peds.2011-3552. Epub...

使用中は授乳中止を検討、あるいは授乳中の使用に際して慎重に検討すべき医薬品

母乳育児と母親の薬について

新生児における薬物動態に影響する諸因子とその成人レベルに達する時期の目安

乳児への薬剤曝露量決定要因は、薬剤の母乳移行性や母乳摂取量のみならず、乳児の薬剤消化管吸収、薬剤処理能力（肝機能、腎機能など）が大きく関わる。