Excretion into milk

Clenbuterol is secreted into the milk of dairy cows. Following administration of 10 mg/kg bw, concentrations of parent clenbuterol in bovine milk were in the range of 5.5-22.5 ppb. Following treatment with 5 mg/kg bw twice daily, concentrations of parent clenbuterol in bovine milk were in the range of 3-9 ppb. The levels of the parent drug in milk can be directly related to plasma levels, but it is unknown whether metabolites of the drug are also excreted into milk. 

Excretion into breast milk can be a very important route for certain types of foreign compounds, especially lipid-soluble substances, because of the high lipid content in milk. Clearly, newborn animals will be specifically at risk from toxic compounds excreted into milk. For example, nursing mothers exposed to DDT secrete it into their milk, and the infant may receive a greater dose, on a body-weight basis, than the mother. Also, because the pH of milk (6.5) is lower than the plasma, basic compounds may be concentrated in the fluid. 

Excretion into milk is important for exposure of the newborn animal. 

In rodents, placental transfer of CDDs to the fetus is relatively limited, but transfer during sensitive periods of organogenesis is biologically important as evidenced by effects on fetuses or offspring exposed in utero. Excretion into milk represents a major pathway for maternal elimination of CDDs and, therefore, for exposure to offspring. In C57BL/6N mice administered a single oral dose of 30 g 14C-... 

This information is provided in the ICH-Guideline S3B Pharmacokinetics Guidance for repeated dose distribution studies (CPMP/ICH/395/95) . Other relevant kinetic questions are the investigations of the potential of compounds to penetrate the barriers of placenta, blood-brain or excretion into milk. 

Volatile chemicals are transported by passive diffusion from the blood into the lungs prior to exhalation. Excretion into milk is important for exposure of the newborn animal. 

Dexmedetomidine is a Pregnancy Category C agent and its use during pregnancy, labor and delivery, including cesarean section deliveries, is not recommended. It is also excreted into milk in animal studies and caution should be used in nursing women. 

Unchanged p,p -DDT tends to be lost only very slowly by land vertebrates. There can, however, be a certain amount of excretion by females into milk or across the placenta into the developing embryo (mammals) or into eggs (birds, reptiles, and insects). 

In terrestrial animals, cyclodienes such as dieldrin, like other refractive lipophilic pollutants, can be excreted in their unchanged forms, notably with lipoproteins, which are exported into milk (mammals), eggs (birds, reptiles, insects), or developing... 

In a review of data on occupational chemicals that may contaminate breast milk (Byczkowski et al. 1994), it is stated that lead may be excreted in milk in amounts lethal to the infant and that the metal may be mobilized from bone stores to milk during the lactation period. Even when the concentration of lead in mother s milk is low, the absorption of metals into the systemic circulation of infants is generally high when they are on a milk diet. To better understand the sensitivity of the nursing infant to chemicals, epidemiological studies, chemical monitoring, and model development and application are needed. 

Ito S, Lee A Drug excretion into breast milk -Overview. Adv Drug Deliv Rev 2003 55 617-627. 

Some minor routes of excretion exist sweat, hair, saliva, semen, milk. While these routes out of the body do not count for much as excretory processes, excretion of some chemicals into milk can be important because it constitutes an exposure pathway for infants, if the milk is from their mothers, and for many people if it is from dairy cattle. Many fat-soluble chemicals follow this pathway out of the body, dissolved in the fatty portion of the milk. Excretion of chemicals through milk is common enough to prompt considerable attention from toxicologists. 

Lactation Vitamin B-12 is excreted into breast milk. 

Lactation Quinidine is excreted into breast milk with a milkiserum ratio of approximately 0.71. The American Academy of Pediatrics considers quinidine to be compatible with breast-feeding. 

Lactation It is not known whether darifenacin is excreted into human milk. Use caution before administering to a breastfeeding woman. 

Lactation Meprobamate is excreted into breast milk at concentrations 2 to 4 times that of maternal plasma. 

Pregnancy Category D- amitriptyline, imipramine, nortriptyline Category C -amoxapine, clomipramine, desipramine, doxepin, protriptyline, trimipramine). Lactation These agents are excreted into breast milk in low concentrations. 

Lactation It is unknown whether or not duloxetine and/or its metabolites are excreted into human milk. Breast-feeding while taking duloxetine is not recommended. 

Lactation Metoclopramide is excreted into breast milk and may concentrate at about twice the plasma level at 2 hours postdose. There appears to be no risk to the nursing infant with maternal doses less than or equal to 45 mg/day. 

B. Lipid-soluble molecules are more likely to be excreted in breast milk because it is primarily a passive diffusion process. A, C, and D are not correct because they are opposite of the typical characteristics of drugs excreted into breast milk. 

POlOO Faber, P., and A. Strenge-Hesse. Reh evance of rhein excretion into breast milk. Pharmacology 1988 l(Suppl 36) 212-220. 

Chlorpromazine is 92 to 97% bound to plasma proteins, principally albumin [5,20], It crosses the blood-brain barrier, and concentrations of the drug in the brain are higher than those in plasma [17], The relationship of plasma concentration to clinical response and toxicity has not been clearly established. Chlorpromazine and its metabolites cross the placenta and are distributed into milk [21]. About 10-12 metabolites of chlorpromazine in humans have been identified. In addition to hydroxylation at positions 3 and 7 of the phenothiazine nucleus, the N-dimethylaminopropyl side chain of chlorpromazine undergoes demethylation and is metabolized to an N-oxide or sulfoxide derivative. These metabolites may be excreted as their 0-glucouronides, with small amounts of ethereal sulfates of the mono- and dihydroxy derivatives. The major metabolites found in urine are the monoglucouronide of N-demethylchlorpromazine and 7-hydroxychlorpromazine [2]. Although the plasma half life of chlorpromazine itself has been reported to be few hours, the elimination of metabolites may be very prolonged [8, 22-24]. 

Penicillin concentrations in most tissues are equal to those in serum. Penicillin is also excreted into sputum and milk to levels 3-15% of those in the serum. Penetration into the eye, the prostate, and the central nervous system is poor. However, with active inflammation of the meninges, as in bacterial meningitis, penicillin concentrations of 1-5 mcg/mL can be achieved with a daily parenteral dose of 18-24 million units. These concentrations are sufficient to kill susceptible strains of pneumococci and meningococci. 

Despite the fact that most drugs are excreted into breast milk in amounts too small to adversely affect neonatal health, thousands of women taking medications do not breast-feed because of misperception of risk. Unfortunately, physicians contribute heavily to this bias. It is important to remember that formula feeding is associated with higher morbidity and mortality in all socioeconomic groups. 

The substrates for milk synthesis enter the secretory cell across the basal membrane (outside), are utilized, converted and interchanged as they pass inwards through the cell and the finished milk constituents are excreted into the lumen across the lumenal or apical membrane. Myoepithelial cells (spindle shaped) form a basket around each alveolus and are capable of contracting on receiving an electrical, hormonally mediated, stimulus, thereby causing ejection of milk from the lumen into the ducts. 

In addition to teratogenicity, mercury has been associated with decreased reproductive performance in quail (123) and lead with neuro-pathological changes in the suckling rat (124). Both inorganic and organic mercury are excreted into the milk with equal ease (121). Fluoride is known to be excreted by the lactating breast as well (78). 

Emodin is partly absorbed and is excreted into the urine and milk (laxative effects on sucklings). The drugs containing emodin color the urine yellowish-brown when it is acid, and reddish or violet when alkaline. It is advisable to warn the patient about this color change. 

The manufacturers of zaleplon advise that it should not be given to breastfeeding mothers since, although only a small amount is excreted into breast milk, the effect on the nursing infant is not known. Zaleplon was... 

Kava has been shown to alter uterine tone in vitro and should be avoided during pregnancy. Kavalactones are soluble and excreted into breast milk. Women who are nursing should avoid kava. 

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