title: Pharmacokinetics of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate. 2nd communication: tissue levels and enzyme activity in rats after repeated administration, and placental and milk transfer after single administration.
abstract: The absorption, distribution and excretion of radioactivity in rats were studied during and after repeated oral administration of 30 mg/kg of NS-21 ((+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate, CAS 129927-33-4) once a day for 21 days. The plasma concentrations of radioactivity 24 h after each administration of 14C-NS-21 reached a steady state on the 5th day. 48 h after the 21st administration, the plasma concentrations of radioactivity were under the detection limit. The plasma concentrations of the radioactivity after the 7th oral administration of 14C-NS-21 was higher than that after the single administration, but similar to those after the 14th and 21st administrations. There were no marked differences in the elimination half-lives after each administration. The urinary and fecal excretion of the radioactivity was 21.5 and 81.3%, respectively, within 168 h after the 21st administration. In most tissues, no radioactivity was observed 336 h after the 21st administration. Repeated oral administration of 30 and 100 mg/kg of NS-21 once a day for 7 days had no effect on the cytochrome P-450 content, aniline hydroxylase and aminopyrine N-demethylase activity in rat liver. The transfer of radioactivity into fetuses and milk was investigated after single oral administration of 14C-NS-21 to female rats. In the 18th day pregnant rats, the radioactivity concentrations were lower in most fetal tissues than in the maternal plasma. After oral administration of 14C-NS-21 to lactating rats, the concentrations of radioactivity were higher in the milk than in the maternal plasma during an 8-h period. No radioactivity was observed in milk 48 h after administration.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Hirota
authors.forename: K
authors.initials: K
authors.lastname: Sugihara
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Tougou
authors.forename: A
authors.initials: A
authors.lastname: Morino
authors.forename: Y
authors.initials: Y
authors.lastname: Ezumi
authors.forename: M
authors.initials: M
authors.lastname: Takaichi
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001345:Autoradiography; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D004790:Enzyme Induction / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D005260:Female; D005333:Fetus / Q000378:metabolism; D007408:Intestinal Absorption; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008892:Milk / Q000378:metabolism; D010648:Phenylacetates / Q000493:pharmacokinetics*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010648:Phenylacetates; C105354:temiverine