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  • Title: The pharmacokinetics of nitrendipine. II. Distribution to and elimination from organs and tissues of rats and dogs after single or repeated administration of [14C]nitrendipine.
    Author: Krause HP, Ahr HJ, Siefert HM, Steinke W, Suwelack D.
    Journal: Arzneimittelforschung; 1988 Nov; 38(11):1599-604. PubMed ID: 3214443.
    Abstract:
    [14C]nitrendipine (3-ethyl 5-methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate, Bay e 5009, Baypress, Bayotensin) was administered to male rats, pregnant and lactating female rats, and female dogs intravenously or orally once as well as to male rats repeatedly over a period of 4 weeks (rat 5 (and 10) mg/kg, dog approximately 3 mg/kg). The distribution of radioactivity (unchanged compound and metabolites) was investigated using whole-body autoradiography as well as quantitative measurements of the organ and tissue concentrations of radioactivity after necropsy. [14C]nitrendipine was distributed rapidly and heterogeneously into the organs and tissues of rats. Already 24 h after administration most of the radioactivity had reached the gastro-intestinal (GI) tract via biliary secretion. High concentrations were also detectable in liver and kidneys. The radioactivity was eliminated from the tissues with terminal half-lives lying between 52 (plasma) and 360 h (muscle). Only 0.13% of the administered radioactivity was detectable in the body (excl. GI-tract) after 10 days. In dogs, the distribution pattern was similar to that observed in rats. After 28 daily administrations of [14C]nitrendipine to male rats the plasma and tissue equivalent concentrations were 3 (plasma) to 12 times (adipose tissue) higher than after single administration. The half-lives were increased by 20 to 70%, lying between 2 and 15 days. There were no indications for any specific retention of the radioactivity. The radioactivity from [14C]nitrendipine was secreted into the milk of lactating rats and crossed the placental barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
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