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Titolo:
Placental transfer and pharmacokinetics of a single oral dose of [C-14]p-nitrophenol in rats
Autore:
Abu-Qare, AW; Brownie, CF; Abou-Donia, MB;
Indirizzi:
Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 Pharmacol & Canc Biol, Durham, NC 27710 USA
Titolo Testata:
ARCHIVES OF TOXICOLOGY
fascicolo: 7, volume: 74, anno: 2000,
pagine: 388 - 396
SICI:
0340-5761(200009)74:7<388:PTAPOA>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTITUTED PHENOLS; PARATHION; PREGNANCY; HYDROXYLATION; DISPOSITION; NITROPHENOL; METABOLISM; TOXICITY; INVITRO; RABBIT;
Keywords:
p-nitrophenol; placental transfer; pharmacokinetics; metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Abou-Donia, MB Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 c Biol, Durham, NC 27710 USA
Citazione:
A.W. Abu-Qare et al., "Placental transfer and pharmacokinetics of a single oral dose of [C-14]p-nitrophenol in rats", ARCH TOXIC, 74(7), 2000, pp. 388-396

Abstract

The pharmacokinetics and placental transfer of a single oral dose of 100 mg/kg (10 mu Ci/kg, 16% of acute oral LD50) Of uniformly phenyl-labeled [C-14]p-nitrophenol were investigated in pregnant Sprague-Dawley rats at 14-18 days of gestation. Three animals were killed on gestation day 18, at 0.5, 1, 2, 4, 12, 24, and 48 h after dosing. Radioactivity was rapidly absorbed and distributed throughout the maternal and fetal tissues. The gastrointestinal tract contents retained 20% and 2% of the dose at 0.5 h and 4 h after dosing. The peak maternal plasma concentration of radioactivity (mu g p-nitrophenol equivalent/ml) was 7.17 compared with 0.37 for fetal plasma at 0.5 h. Maximum concentration of radioactivity (mu g p-nitrophenol equivalent/g fresh tissue) was detected in most tissues 0.5 h after closing and was in descending order: kidney 23.27, liver 12.37. placenta 3.56, fetus 2.17, and brain 1.99. Radioactivity was eliminated from plasma and all tissues briexponentially. The half-lives of elimination of C-14 were 34.65 h and 69.30 h for maternal and fetal plasma, respectively. p-Nitrophenol, detected by HPLC, was the major compound identified in plasma and tissues. While p-nitrophenol disappeared biphasically from maternal plasma and kidney, it was eliminated monophasically from brain, placenta, and liver. p-Nitrocatechol and p-aminophenol concentrations were detected in the liver with peak at 0.5 h of 1.13 and 1.00 mu g/g fresh tissue, respectively. While the change in the concentration of p-nitrocatechol with 1 time was monophasic, that of p-aminophenol showed a biphasic pattern with elimination half-lives of 1.93 h and4.95 h, respectively. Radioactivity was rapidly excreted in the urine mostly as polar metabolites, while only 3% of the dose was recovered in the feces. Radioactive materials excreted in the urine comprised: glucuronides 4%,sulfates 8%, hot-acid hydrolysates 11%, nonconjugated compounds 16%. and water-soluble metabolites 61%. This study demonstrated that although orally administered p-nitrophenol is a rapidly absorbed and excreted compound, it is transported to the maternal brain and the fetus and may pose a health risk following exposure to toxic doses during pregnancy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 04:24:23