Impairment of estramustine phosphate absorption by concurrent intake of milk and food

The effect of milk and food on the pharmacokinetics of estramustine phosphate was investigated in six patients with prostatic cancer. In a randomized three-way cross-over study, the patients were given single doses of the drug together with low calcium water, low calcium food and milk. The evaluatio...

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Bibliographic Details
Published in:European journal of clinical pharmacology 1990-01, Vol.38 (2), p.189-193
Main Authors: GUNNARSSON, P. O, DAVIDSSON, T, ANDERSSON, S.-B, BACKMAN, C, JOHANSSON, S.-A
Format: Article
Language:English
Subjects:
Aged
Animals
Antineoplastic agents
Biological and medical sciences
Biological Availability
Chromatography, Gas
Estramustine - pharmacokinetics
Estramustine - therapeutic use
Estrone - pharmacokinetics
Food
General aspects
Humans
Male
Medical sciences
Middle Aged
Milk
Nitrogen Mustard Compounds - pharmacokinetics
Pharmacology. Drug treatments
Prostatic Neoplasms - drug therapy
Radioimmunoassay
Random Allocation
Solubility
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Summary:The effect of milk and food on the pharmacokinetics of estramustine phosphate was investigated in six patients with prostatic cancer. In a randomized three-way cross-over study, the patients were given single doses of the drug together with low calcium water, low calcium food and milk. The evaluation was based upon the plasma concentration of two metabolites, estromustine and estrone, as parent drug could not be detected in plasma. The tmax and lag time of estromustine were significantly increased by milk and food intake and Cmax and AUC were significantly decreased. In comparison with water, the AUC of estromustine was 41% when the drug was taken with milk and 67% after simultaneous intake of standardized food. Corresponding figures for the peak values were 32 and 57%, respectively. The effect of milk and food intake on the pharmacokinetics of estrone was similar. Studies in vitro demonstrated that the dissolution of estramustine phosphate disodium was markedly impaired in the presence of calcium. It was concluded that the rate and extent of absorption of estramustine phosphate were decreased when the drug was taken with milk or food due to the formation of a poorly absorbable calcium complex. To obtain high and reproducible absorption of Estracyt, the drug should not be taken together with milk, milk products or other calcium-rich food or drugs.
ISSN:0031-6970
1432-1041
DOI:10.1007/BF00265983