title: Metabolism, excretion, and pharmacokinetics of S-allyl-L-cysteine in rats and dogs.
abstract: The metabolism, excretion, and pharmacokinetics of S-allyl-l-cysteine (SAC), an active key component of garlic supplements, were examined in rats and dogs. A single dose of SAC was administered orally or i.v. to rats (5 mg/kg) and dogs (2 mg/kg). SAC was well absorbed (bioavailability >90%) and its four metabolites-N-acetyl-S-allyl-l-cysteine (NAc-SAC), N-acetyl-S-allyl-l-cysteine sulfoxide (NAc-SACS), S-allyl-l-cysteine sulfoxide (SACS), and l-γ-glutamyl-S-allyl-l-cysteine-were identified in the plasma and/or urine. Renal clearance values (<0.01 l/h/kg) of SAC indicated its extensive renal reabsorption, which contributed to the long elimination half-life of SAC, especially in dogs (12 hours). The metabolism of SAC to NAc-SAC, principal metabolite of SAC, was studied in vitro and in vivo. Liver and kidney S9 fractions of rats and dogs catalyzed both N-acetylation of SAC and deacetylation of NAc-SAC. After i.v. administration of NAc-SAC, SAC appeared in the plasma and its concentration declined in parallel with that of NAc-SAC. These results suggest that the rate and extent of the formation of NAc-SAC are determined by the N-acetylation and deacetylation activities of liver and kidney. Also, NAc-SACS was detected in the plasma after i.v. administration of either NAc-SAC or SACS, suggesting that NAc-SACS could be formed via both N-acetylation of SACS and S-oxidation of NAc-SAC. In conclusion, this study demonstrated that the pharmacokinetics of SAC in rats and dogs is characterized by its high oral bioavailability, N-acetylation and S-oxidation metabolism, and extensive renal reabsorption, indicating the critical roles of liver and kidney in the elimination of SAC.
authors: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima, Japan amano_h@wakunaga.co.jp.
authors: Hirotaka
authors: H
authors: Amano
authors: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima, Japan.
authors: Daichi
authors: D
authors: Kazamori
authors: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima, Japan.
authors: Kenji
authors: K
authors: Itoh
authors: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Hiroshima, Japan.
authors: Yukihiro
authors: Y
authors: Kodera
mesh_terms: D000107:Acetylation; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C054604:N-acetyl-S-allylcysteine; C065299:S-allylcysteine; D003545:Cysteine