@article {Han221, author = {Kye S. Han and Myung G. Lee}, title = {Pharmacokinetics of a Chemoprotective Agent, 2-(Allylthio)pyrazine, after Intravenous and Oral Administration to Rats: Hepatic and Gastric First-Pass Effects}, volume = {27}, number = {2}, pages = {221--226}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Pharmacokinetic parameters of 2-(allylthio)pyrazine (2-AP) were evaluated after i.v. administration of the drug (10, 20, 50, and 100 mg/kg body weight) and oral administration of the drug (10, 50, and 100 mg/kg body weight) to rats. The hepatic, gastric, and intestinal first-pass effects of 2-AP were also measured after i.v., intraportal, intraduodenal, and oral administration of the drug (10 and 50 mg/kg body weight) to rats. After i.v. administration, the pharmacokinetic parameters of 2-AP were dose-independent at the dose ranges studied. However, after oral administration, the dosenormalized total area under the plasma concentration-time curve from time zero to time infinity values (43.5, 125, and 205 μg min/ml, based on 10 mg/kg body weight) increased significantly with increasing doses. The extent of absolute oral bioavailability (F) values also increased with increasing oral doses; the values were 19.6, 56.7, and 93.6\% for 10, 50, and 100 mg/kg body weight, respectively. The oral data above could be due to saturable hepatic, gastric, and/or intestinal first-pass effects. This was proved by saturable gastric first-pass effect (the significant area under the plasma concentration-time curve from time zero to time infinity difference between oral and intraduodenal administration of 2-AP); the values were 62.6 and 26.6\% at 2-AP doses of 10 and 50 mg/kg body weight, respectively. Approximately 20\% of oral dose was eliminated by liver (hepatic first-pass effect) for both oral doses of 10 and 50 mg/kg body weight. However, the first-pass effects of 2-AP in the intestine, heart, and lung were almost negligible. The low F value after oral administration of 2-AP at low dose (10 mg/kg body weight) was mainly due to gastric first-pass effect in rats. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/27/2/221}, eprint = {https://dmd.aspetjournals.org/content/27/2/221.full.pdf}, journal = {Drug Metabolism and Disposition} }