Tissue distribution of phenoxybenzamine in the rat. Lack of adipose tissue storage.
Rats were given the basic lipophilic drug, phenoxybenzamine, in single i.v. doses of 0.4 and 30 mg/kg. The drug was determined in plasma and 7 tissues by a new HPLC method. Adipose tissue reached peak levels after 30 minutes. At that time levels in heart, kidney, and brain were higher than in subcutaneous, epididymal, and mesenteric adipose tissues. The percentage metabolites in adipose tissue, kidney, and liver was 0, 88, and 96, respectively. Pretreatment with SKF 525-A inhibited metabolism and increased the tissue levels of unchanged drug, however, even under these conditions storage in adipose tissues did not occur, the adipose storage index being still less than unity. These results contradict findings of the 1950s which have been repeatedly reported in textbooks and reviews, but they confirm observations that basic drugs, even when highly lipophilic, are not being stored in adipose tissues.
Moor
M J
MJ
Department of Pharmacology, University of Bern, Switzerland.
Bickel
M H
MH
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010643:Phenoxybenzamine / Q000493:pharmacokinetics*; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D010643:Phenoxybenzamine; D011335:Proadifen