Breast milk elimination

Phenytoin s absorption is slow and variable yet almost complete absorption eventually occurs after po dosing. More than 90% of the dmg is bound to plasma protein. Peak plasma concentrations are achieved in 1.5—3 h. Therapeutic plasma concentrations are 10—20 lg/mL but using fixed po doses, steady-state levels are achieved in 7—10 days. Phenytoin is metabolized in the fiver to inactive metabolites. The plasma half-life is approximately 22 h. Phenytoin is excreted primarily in the urine as inactive metabolites and <5% as unchanged dmg. It is also eliminated in the feces and in breast milk (1,2). Prolonged po use of phenytoin may result in hirsutism, gingival hyperplasia, and hypersensitivity reactions evidenced by skin rashes, blood dyscrasias, etc... 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

Renal excretion is the most important endosulfan elimination route in humans and animals. Biliary excretion has also been demonstrated to be important in animals. Estimated elimination half-lives ranged between approximately 1 and 7 days in adult humans and animals. Endosulfan can also be eliminated via the breast milk in lactating women and animals, although this is probably a relatively minor elimination route. No studies were located regarding known or suspected differences between children and adults with respect to endosulfan excretion. 

No data were located concerning whether pharmacokinetics of endosulfan in children are different from adults. There are no adequate data to determine whether endosulfan or its metabolites can cross the placenta. Studies in animals addressing these issues would provide valuable information. Although endosulfan has been detected in human milk (Lutter et al. 1998), studies in animals showed very little accumulation of endosulfan residues in breast milk (Gorbach et al. 1968 Indraningsih et al. 1993), which is consistent with the rapid elimination of endosulfan from tissues and subsequent excretion via feces and urine. There are no PBPK models for endosulfan in either adults or children. There is no information to evaluate whether absorption, distribution, metabolism, or excretion of endosulfan in children is different than in adults. 

The main rout of excretion of the drug and its metabolites is the kidney with a half-life of 9-18 h in human. In contrast to human, animal models have a lower elimination half-life ranging from 0.6-9 h [78]. The elimination half-life of valproic acid and some metabolites was found to be much longer in the neonates (40-50 h) than adult subjects (9-18 h) [78,81]. One study reported no difference between the elimination half-life between elderly and young subjects (15.4 and 13.0 h, respectively) while other found an increase in for older patients (14.9 versus 7.2 h for young patients) [78,90], Insignificant amounts of valproic acid are found in breast milk, approximately 3% of maternal drug levels [84]. 

Absorption occurs through the respiratory tract, orai membranes, and skin (Taylor 1996). Absorption from the stomach is iimited, uniess the acidity is reduced, because nicotine is a strong base. Between 80 and 90% of nicotine is metabolized, mainly in the liver but also the kidneys and lungs. Cotinine is the primary metabolite of nicotine, and the half-life of nicotine is about 2 hours. Elimination occurs by the kidneys, but it is also present in the breast milk of lactating women. 

Benign Not evident while sole nutrition is breast milk Severe hypoglycemia and lactic acidosis after fructose ingestion Vomiting, apathy, diarrhea Liver damage and jaundice Proximal renal tubule disorder resembling Fanconi syndrome Treatment eliminate sources of fructose from diet... 

Chemicals and/or their metabolites are eventually eliminated. The three organs predominantly involved in elimination are the liver, the lungs, and the kidneys. Other routes of excretion include bile, feces, sweat, saliva, breast milk, nails, and hair. 

It is excreted in breast milk at concentration constantly higher than those in maternal plasma. The elimination of pseudoephedrine is reduced in renal impairment. Hepatic dysfunction is unlikely to affect the pharmacokinetics of the drug. 

Lithium enters breast milk in concentrations equal to those in maternal serum. Clearance of this drug is almost completely dependent upon renal elimination, and women who are receiving lithium may expose the infant to relatively large amounts of the drug. 

After oral administration, nevirapine is rapidly absorbed with a bioavailability of 93%, and peak plasma concentrations are achieved in 4h. Food or antacids do not interfere with its absorption. It is very lipophilic, crosses the placenta and its presence has been reported in breast milk. Nevirapine is mainly metabolized by the cytochrome P-450 system (CYP3A4 and CYP2B6) to hydroxy-lated metabolites, and after metabolism, the primary route of excretion is through urine. It has an elimination half-life of 25-30 h. Nevirapine can induce its own metabolism by stimulating the cytochrome P-450 system, which results in the reduction of the half-life of subsequent doses. In combination with other antiretroviral agents, nevirapine is recommended for the treatment of HIV infection in adults and children. It should not be administered alone since resistance develops rapidly. 

One elimination route that is of importance to a specific type of patient is breast milk. Nursing mothers must be very careful when taking medication because many drugs are eliminated, at least partially, through breast milk. A mother may unintentionally serve as a drug administration vehicle for her nursing child. 

Evidence is similar for humans but limited, and includes male sterility, spontaneous abortions in human females, premature human fetuses, severe neurologic and CNS effects, blood dyscrasias, hepatotoxicity, accumulation of organohalogen pesticides in human lipid tissue—and, perhaps even more important, their presence in human breast milk, whence they can continue to exert influences on growth, development and hormonal, CNS and enzyme systems. Aldrin, dieldrin, chlordane, chlordecone (Kepone), heptachlor epoxide, hexachlorobenzene (HCB) and Mirex are all excreted via breast milk in the human female. This is also true for the related PCBs and PBBs that resist biodecomposition and maintain persistent residence in mammalian tissues. For them, excretion via breast milk may constitute the main—if not sole—elimination route. 

For people, the average time it takes to remove one-half of the 2,3,7,8-TCDD from the body is highly variable and may take from 7 to 12 years. There is less information on the other CDDs, but what information exists suggests 5 to 15 years. CDDs are eliminated from the body primarily in the stool, and only a small amount leaves the body in the urine. Some CDDs will leave the body in the breast milk of nursing mothers. 

Limited information was located regarding reducing body burden following exposure to CDDs in humans. A recent study examined the influence of short-term dietary measures on CDD and CDF concentrations in human milk (Pluim et al. 1994c). The authors hypothesized that mobilization of fatty acids from adipose tissue cause the concomitant release of CDDs and CDFs, which will then be eliminated in the breast milk. Two diets were tested for their ability to reduce the concentration of CDDs... 

Elimination of milk formula in infants lasts for at least 2 weeks. In this period, the infants are given extensively hydrolyzed casein or whey-based formulas. If they refuse to drink such formulas, adverse food reactions to these are suspected. The child should receive elementary (amino-acid) formula. If a breast-fed infant is suspected of hypersensitivity to cow s milk product or other food(s) via breast milk, the mother is also requested to temporarily avoid these products (Lifschitz, 2005). 

Nimodipine is excreted in feces via the bile duct, and in urine via the glomular filtration, as metabolites [1, 10]. Fecal excretion is the major excretory route (greater than 67%) [11], The parent compound and its metabolites were detected in breast milk [9]. The average elimination half-life for the drug is reported to be 9 h, but the initial decline in plasma is much more rapid, equivalent to a half-life of 12 h [1], An average of 43% of bile-excreted nimodipine is subject to pronounced enterohepatic... 

Regarding human health risks the Deca risk assessors note that scientific information on bioconcentration in human adipose tissues and subsequent elimination via for example breast milk is insufficient, but that other brominated diphenyl ethers (i.e. Hexa, Penta and Tetra) are excreted with breast milk. Based on the low rate of oral absorption in rats and the low bioaccumulation potential, the Deca risk assessors state that they might anticipate a rather low excretion of this compound in the breast milk. ... 

Some toxic agents such as Pb, Hg, other heavy metals, and many organic substances are excreted in the bile as conjugates to the intestinal tract for elimination in the feces. Other common routes of elimination include the lungs for gaseous (e.g., NH3) and volatile toxicants (e.g., alcohol, sweat, tears, and saliva), as well as breast milk and eggs in females. 

As well as excretion into urine, bile, and expired air, chemicals, especially those that are very soluble in fat, can be eliminated into breast milk. It can be shown that DDT, for example, is sometimes present in samples of human breast milk. This is potentially very significant as it exposes the newborn baby to chemicals, some of which may be harmful and present in concentrations sufficient to cause effects. 

Elimination of Tl is mainly through the gastrointestinal tract but elimination also occurs through the kidneys, saliva, hair, skin, sweat, and breast milk. Relative amounts excreted by each route vary by species. Thallium is likely excreted through intestinal and gastric secretions associated with potassium loss or excretion. Likewise, reabsorption of Tl also occurs, mainly from the colon. The estimated biological half-life of Tl is 10 days but values up to 1 month have been reported (WHO, 1996). 

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