Milk-plasma ratio

Milk. The study of passage of a xenobiotic into milk serves to assess the potential risk to breast-fed infants in the absence of human data. The passage into milk can be estimated as the milk plasma ratio of drug concentrations at each sampling time or... 

Moclobemide was measured in the milk and plasma of six nursing mothers after single oral doses of moclobemide 300 mg, 3-5 days after delivery (16). The milk plasma ratio was 0.72 and the estimated dose of moclobemide to the infant was at most 1.2% of the weight-adjusted maternal dose. 

The Motherisk Team in Toronto has recommended use of the Exposure Index (the maternal milk/plasma ratio times 100 divided by the infants clearance in ml/kg/min-ute) to determine the advisability of breastfeeding when a mother is taking lithium (501). However, this approach does not seem very practical. 

In seven lactating women the mean concentrations of carbamazepine in milk and plasma samples were 15 and 26 pmol/l respectively the concentrations of carbamazepine 10,11-epoxide were 5 and 8 qmol/1 respectively (75). The mean milk/plasma ratios were 0.64 and 0.79 respectively. The amounts of carbamazepine and carbamazepine 10,11-epoxide that a breast-feeding child is likely to consume are thus very small. 

Postpartum depression is a relatively common occurrence in women after childbirth. One female who started taking 300 mg of St. John s wort (Jarsin 300) three times daily after meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive episode 5 months after delivery agreed to have milk samples tested. Hypericin was not detected in the milk samples, but hyperforin was detected at low concentrations, with higher levels in the hind-milk than the foremilk samples. The milk/plasma ratio was well below one for both hypericin and hyperforin. Both levels were undetectable in the infant s serum and the baby showed no negative side effects... 

General regression neural network (GRNN) was introduced by Donald Specht in 1991 [33], and it has been successfully used in pharmacokinetic studies, including human intestinal absorption [34], blood-brain barrier prediction [35], human serum albumin binding [35], milk-plasma ratio [35], and drug clearance [36], Recently it has been applied for the prediction of Tetrahymenapyriformis toxicity [37],... 

Wilson, J. T., et al. (1985). Pharmacokinetic pitfalls in the estimation of the breast milk/plasma ratio for drugs. Annual Review of Pharmacology and Toxicology, 25, 667—689. 

Caution use only if necessary during pregnancy (Pregnancy Category B) and lactation. The clinical effects on humans during pregnancy and nursing have not been studied. Lidocaine crosses the placenta and is known to be secreted in milk at a milk/plasma ratio of 0.4/1. Lidoderm use in the pediatric population has not been studied and is not recommended. 

Antipsychotics appear in breast milk with milk-to-plasma ratios of 0.5 to 1, however, 1-week post-delivery, clozapine milk concentrations were found to be 279% of serum concentrations. Use of clozapine during breast-feeding is not recommended. 

Lactation Lovastatin and atorvastatin are excreted in the milk of rats atorvastatin is likely to be excreted in breast milk it is not known whether lovastatin, rosuvastatin, and simvastatin are excreted in breast milk a small amount of pravastatin is excreted in breast milk fluvastatin is present in breast milk in a 2 1 ratio (milk plasma). 

In general, the macrolides are administered orally but sometimes also paren-terally. All the members of this group are well absorbed and are distributed extensively in tissues, especially in the lungs, liver, and kidneys, with high tissue to plasma ratios. They are retained in the tissues for long periods after the levels in the blood have ceased to be detectable. Elimination of all macrolides occurs primarily through hepatic metabolism, which accounts for approximately 60% of an administered intravenous dose the remainder is excreted in active form in the urine and bile. With oral and intramuscular administration, urinary excretion decreases, but biliary excretion and hepatic metabolism increase proportionally. Milk has often macrolide concentrations severalfold greater than in plasma (7). 

Table 7 Comparison of calculated and experimentally obtained milk plasma concentration ratios for antimicrobial agents under equilibrium conditions...

The concentrations of topiramate have been measured in plasma and breast milk in five women with epilepsy during pregnancy and lactation (52). The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of topiramate. The mean milk/maternal plasma concentration ratio was 0.86 (range 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar. Two of the breast-fed infants had detectable (>0.9 pmol/l) concentrations of topiramate 2-3 weeks after delivery, although they were below the limit of quantification (2.8 pmol/l), and one had an undetectable concentration. Thus, breastfed infants had very low topiramate concentrations. No adverse effects were observed in the infants. 

Because the safe use of carbamazepine during pregnancy has not been established, caution should be used in prescribing carbamazepine during the first trimester of pregnancy or in women of reproductive age. Carbamazepine may cause craniofacial deformities, spina bifida (0.5% to 1%), and low birth weight. Carbamazepine is excreted in breast milk (the milk-to-maternal plasma ratio of carbamazepine is about 0.4)." There are two case reports of transient cholestatic hepatitis and jaundice in nursing infants. 

TABLE 2.3 Milk Plasma Concentration Ratios of AMDs in Lactating Cows ... 

In two mothers, the placental transfer at time of birth, and breast milk concentrations after birth, of vigabatrin enantiomers were examined [172]. Both women had measurable concentrations of vigabatrin in the cord and maternal venous blood. The umbilical vein maternal vein concentrations ranged widely from 7% to 139% in the two women, although the ratios were greater for the R enantiomer than for the S enantiomer in both women. In the breast milk, the level of stereoselectivity was similar to that found in cord blood. The milk plasma concentration ratios of the enantiomers were... 

At the lower pH of milk, the ratio between milk and plasma for weak organic bases (such as antibiotics erythromycin and tylosin) is >1, while for organic acids (benzylpenicillin, sulfadimethoxin) it is < 1. For example, during mammary gland tissue inflammation (mastitis), the pH of milk increases and this ratio of the organic bases decreases. Specific examples are given in Table 12.69. 

In milk, the concentration of SDM and its metabolites was a reflection of those in plasma (14 Figure 4). The disposition of SDM in plasma, edible tissues, bile and urine of calves are illustrated in Figure 5. As shown, the SDM concentration in plasma was higher than that in the edible tissues. The latter is also confirmed by the tissue to plasma concentration ratios of SDM and its metabolites which were lower than 1, except for the metabolite ratios in kidney tissue (Table II). The SCH2OH concentration in the kidney exceeded those of SDM (Figure 6). The N -SDM metabolite concentrations in muscle, kidney and liver were always below those of SDM (Table II ... 

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