Drug Distribution Within Human Milk Phases

The binding of nine drugs of diverse physicochemical characteristics to major human milk whey proteins is reported. This group included acids, bases and neutral drugs. No drug bound to alpha‐lactalbumin, which is the protein present in greatest concentrations in mature milk. Four drugs, diclofenac, phenytoin, prednisolone and warfarin, bound to albumin but to a much lesser extent than in plasma, consistent with quantitatively less albumin in milk. None of the basic drugs studied bound to albumin. Five drugs, atenolol, diclofenac, prednisolone, propranolol and warfarin, bound to lactoferrin though the extent was minimal except for diclofenac. This group included acids, bases and neutral drugs.

Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

The binding of drugs to major human milk whey proteins.

Atkinson

Begg

1988

“…The fat content of milk was 3.4, 7.9 and 12.5%; that of protein 1.9, 3.0 and 6%. Increased milk protein resulted [14,15] = TBq mmol'; ? = no data for % binding.…”

Section: Resultsmentioning

confidence: 99%

“…In theory, increasing milk fat would aid the sequestration of a lipid soluble drug into milk and increasing protein would enhance the proportion of acidic drug binding in milk. Syversen & Ratkje [14] using in vitro techniques, observed that the lipid solubility of a drug appeared to be the most important property responsible for variations in drug concentration. Our results indicate that fat and protein content should not be seen as individually controlling the transfer of a drug.…”

Section: Discussionmentioning

confidence: 99%

An in vitro technique for the rapid determination of drug entry into breast milk.

Notarianni

Belk

Aird

et al. 1995

“…Because trazodone is a weak base with a pKa of 6.15, it is mostly in the unionized form in plasma (pH 7.4). The theoretical milk/plasma ratio of trazodone may be calculated as follows (Wilson et al, 1980) (Syversen & Ratkje, 1985). These investigators found that lipid solubility of the drug and fat content of milk seem to be important factors determining the distribution of drug in breast milk.…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

Excretion of trazodone in breast milk.

Verbeeck¹,

Ross²,

McKenna³

1986

The excretion of breast milk was studied in six lactating women following the oral administration of a single trazodone tablet (50 mg). The milk/plasma ratio of trazodone based on area under the plasma and milk curves was small: 0.142 ± 0.045 (mean ± s.d.).Assuming that the babies would drink 500 ml 12 h-1, they would be exposed to less than 0.005 mg kg-1 as compared to 0.77 mg kg-1 for the mothers. It is concluded that exposure of babies to trazodone via breast milk is very small.