Pharmacokinetics of 4-acetylaminophenylacetic acid. 2nd communication: tissue accumulation and enzyme induction in rats after repeated administration, and placental and milk transfer after single dosing.
The absorption, distribution, metabolism and excretion of 14C-labeled 4-acetylaminophenylacetic acid (MS-932) were studied in male rats after administration of an oral dose of 10 mg/kg once a day for 21 days. Comparison with the single dosing showed no marked alterations in absorption, distribution, metabolism and excretion. There were no significant differences in the activities of hepatic aniline hydroxylase and aminopyrine N-demethylase between the MS-932 treated group (10 mg/kg for 8 days) and the 0.5% aqueous sodium carboxymethyl cellulose control group (p greater than 0.05). Placental transfer of radioactivity was studied after single oral administration of 10 mg/kg of 14C-MS-932 to pregnant rats on the 12-13th and 19-20th days of gestation. Radioactivity concentrations were highest in the maternal plasma and lowest in the amniotic fluid and fetus for both middle and late pregnancies. The concentrations in the amniotic fluid and fetus decreased more slowly than did the concentration in the maternal plasma. Excretion of radioactivity to milk was studied after single oral administration of 10 mg/kg of 14C-MS-932 to lactating rats on the 10th day after parturition. Radioactivity concentrations in the rat milk were maximal at 1 h after dosing and were lower than in the maternal plasma at all the sampling times.
Sugihara
K
K
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Morino
A
A
Sugiyama
M
M
Iida
S
S
Nomura
A
A
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000815:Aniline Hydroxylase / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology; D001345:Autoradiography; D004790:Enzyme Induction / Q000187:drug effects*; D005243:Feces / Q000737:chemistry; D005260:Female; D005333:Fetus / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D010648:Phenylacetates / Q000493:pharmacokinetics* / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; C052562:4-(acetylamino)benzeneacetic acid; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital