Drug distribution within human milk phases.

Phase distribution and protein binding of drugs in human milk have been measured. The analytical method is reproducible, rapid, and requires only small sample volumes. Five drugs were studied: diazepam, phenobarbital, warfarin, phenytoin, and disopyramide. Experiments were carried out at 37 degrees C on milk samples with variable fat and protein contents. Results for the distribution of drugs between the skimmed-milk phase and fat-rich phase are presented, as well as the results of the dialysis of drugs in skimmed milk. It is shown that, among the physicochemical properties of a drug, the lipid solubility seems to be the most important property for predicting variations in drug concentrations in milk. The potential significance of the findings with respect to in vivo distribution of drugs into human milk is discussed.

Ergotamine in plasma and CSF after i.m. and rectal administration to humans.

An attempt was made to study the kinetics of penetration of ergotamine across the blood-brain barrier. A single therapeutic dose of ergotamine was given to 18 hospitalized patients; eight patients received 0.5 mg i.m., three patients 4 mg rectally, and seven patients 2 mg rectally. Plasma samples were drawn between 0.25 and 72 h and one CSF sample was taken from each patient between 0.5 and 6.5 h after administration. The ergotamine concentrations were measured using a RIA method. The 0.5 mg intramuscular injection showed the highest plasma levels of ergotamine, with a mean peak concentration of 1.27 ng/ml reached at 0.5 h. The 4 mg rectal administration resulted in mean plasma ergotamine levels of 0.44 ng/ml in the time interval of 0.75-2 h. The 2 mg ergotamine rectally resulted in mean plasma levels of 0.15-0.17 ng/ml 1-8 h after administration of ergotamine. Neither the plasma samples taken after 10 h nor the CSF samples had ergotamine concentrations above the detection limit of the RIA method (0.1 ng ergotamine/ml).

Acetazolamide-induced interference with primidone absorption. Case reports and metabolic studies.

Effects of acetazolamide on primidone plasma levels were studied in three patients. Apparent interaction occurred in two patients. Primidone was not detected in the plasma when given orally with acetazolamide in one patient. In another, peak serum concentration was delayed, with corresponding delays in urinary excretion of primidone and metabolites. Plasma and urine concentrations of the two metabolites, phenylethylmalonamide and phenobarbital, were also studied.

Cadmium and zinc in human liver and kidney.

Liver and kidney samples obtained from 76 autopsies were analyzed for cadmium and zinc content. The patients had died of various internal diseases. None of them had any known occupational exposure to cadmium. A record was made of age, sex, place of residence, diagnosis, and smoking habits of each patient. The results showed no significant correlation between cadmium accumulation and hypertension or cardiovascular disease. There was, however, a significantly higher kidney cadmium level in smokers than in nonsmokers.