title: Pharmacokinetics of S-Allyl-l-cysteine in Rats Is Characterized by High Oral Absorption and Extensive Renal Reabsorption.
abstract: BACKGROUND
  S-Allylcysteine (SAC) is a key component of aged garlic extract, one of many garlic products. However, information on its pharmacokinetics has been scant except for data from a few animal studies.
  
  
  OBJECTIVE
  We designed this study to determine the overall pharmacokinetics of SAC in rats.
  
  
  METHODS
  After oral or intravenous administration of SAC to rats at a dose of 5 mg/kg, the plasma concentration-time profile of SAC and its metabolites, as well as the amounts excreted in bile and urine, were analyzed by using liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  After oral administration, SAC was well absorbed with a bioavailability of 98%. Two major metabolites of SAC, N-acetyl-S-allylcysteine (NAc-SAC) and N-acetyl-S-allylcysteine sulfoxide (NAc-SACS), were detected in plasma, but their concentrations were markedly lower than those of SAC. SAC was metabolized to a limited extent, but most of the orally absorbed SAC was excreted into urine in the form of its N-acetylated metabolites. The amounts of SAC, NAc-SAC, and NAc-SACS excreted in urine over 24 h were 2.9%, 80%, and 11% of the orally administered SAC, respectively. The very low renal clearance (0.016 L ⋅ h(-1) ⋅ kg(-1)) of SAC indicated that it undergoes extensive renal reabsorption. These results collectively suggested that SAC was ultimately metabolized to NAc-SAC and NAc-SACS through the cycles of urinary excretion, renal reabsorption, and systemic recirculation.
  
  
  CONCLUSIONS
  The pharmacokinetics of SAC in rats were characterized by high oral absorption, limited metabolism, and extensive renal reabsorption, all of which potentially contribute to its high and relatively long-lasting plasma concentrations.
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Japan amano_h@wakunaga.co.jp.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Amano
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Kazamori
authors.affiliation: Drug Discovery Laboratory, Wakunaga Pharmaceutical Co., Ltd., Akitakata, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000107:Acetylation; D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism; D001682:Biological Availability; D003545:Cysteine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005737:Garlic / Q000737:chemistry*; D007408:Intestinal Absorption; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D065608:Renal Reabsorption
chemical_list: D010936:Plant Extracts; C054604:N-acetyl-S-allylcysteine; C006453:alliin; C065299:S-allylcysteine; D003545:Cysteine
keywords: S-allyl-L-cysteine; aged garlic extract; oral absorption; pharmacokinetics; renal reabsorption