title: Pharmacokinetics and N-acetylation metabolism of S-methyl-l-cysteine and trans-S-1-propenyl-l-cysteine in rats and dogs.
abstract: 1. Pharmacokinetics and N-acetylation metabolism of S-methyl-L-cysteine (SMC) and trans-S-1-propenyl-L-cysteine (S1PC) were examined in rats and dogs. SMC and S1PC (2-5 mg/kg) were well absorbed in both species with high bioavailability (88-100%). 2. SMC and S1PC were excreted only to a small extent in the urine of rats and dogs. The small renal clearance values (<0.03 l/h/kg) indicated the extensive renal reabsorption of SMC and S1PC, which potentially contributed to their long elimination half-lives (>5 h) in dogs. 3. S1PC, but not SMC, underwent N-acetylation extensively in vivo, which can be explained by the relative activities of N-acetylation of S1PC/SMC and deacetylation of their N-acetylated forms, N-acetyl-S1PC/N-acetyl-SMC, in the liver and kidney in vitro. The activities for S1PC N-acetylation were similar to or higher than those for N-acetyl-S1PC deacetylation in liver S9 fractions of rat and dog, whereas liver and kidney S9 fractions of rat and dog had little activity for SMC N-acetylation or considerably higher activities for N-acetyl-SMC deacetylation. 4. Our study demonstrated that the pharmacokinetics of SMC and S1PC in rats and dogs was characterized by high bioavailability and extensive renal reabsorption; however, the extent of undergoing the N-acetylation metabolism was extremely different between SMC and S1PC.
authors.affiliation: a Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd. , Akitakata , Hiroshima , Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Amano
authors.affiliation: a Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd. , Akitakata , Hiroshima , Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kazamori
authors.affiliation: a Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd. , Akitakata , Hiroshima , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D004285:Dogs; D005100:Expectorants / Q000493:pharmacokinetics; D051381:Rats
chemical_list: D005100:Expectorants; D003545:Cysteine; C017507:mecysteine
keywords: Aged garlic extract; bioavailability; renal reabsorption; water-soluble organosulfur compounds