title: The relative bioavailability of the calcium salt of β-hydroxy-β-methylbutyrate is greater than that of the free fatty acid form in rats.
abstract: BACKGROUND
  β-Hydroxy-β-methylbutyrate (HMB) supplementation has been demonstrated to enhance muscle protein synthesis and attenuate loss of muscle mass by multiple pathways. The beneficial effects of HMB have been studied by using either the calcium salt, monohydrate, of HMB (CaHMB) or the free acid form (FAHMB).
  
  
  OBJECTIVE
  The present study was designed to compare the pharmacokinetics and relative bioavailability of the 2 forms of HMB administered as a liquid suspension in male Sprague-Dawley rats.
  
  
  METHODS
  CaHMB at 30, 100, and 300 mg/kg and equivalent doses of FAHMB at 24.2, 80.8, and 242 mg/kg were administered orally as a liquid suspension to male Sprague-Dawley rats. A single i.v. dose of 5 mg/kg CaHMB, corresponding to an equivalent dose of 4.04 mg/kg FAHMB, was also administered. Plasma concentrations of HMB were analyzed by liquid chromatography tandem mass spectrometry, and pharmacokinetic variables and relative bioavailability of the 2 forms of HMB were determined.
  
  
  RESULTS
  After oral administration, the area under the plasma concentration time curve (AUC) from time 0 to time t (0-t) and from time 0 to infinity (0-∞) and the maximum (peak) plasma concentration (Cmax) for CaHMB were significantly greater than for FAHMB, whereas the time to reach Cmax did not differ from that of FAHMB. The relative bioavailability of CaHMB was 49%, 54%, and 27% greater than that of FAHMB for the 3 respective oral doses tested. After i.v. administration, the AUCs 0-t and 0-∞ of the calcium salt were significantly greater than those of FAHMB. The relative bioavailability of CaHMB was 80% greater than that of FAHMB. The higher relative bioavailability of CaHMB may be attributable to its low systemic clearance compared with FAHMB.
  
  
  CONCLUSIONS
  This study demonstrates the enhanced relative bioavailability of CaHMB compared with FAHMB. Further studies are warranted to understand the physiologic mechanisms contributing to the differences in systemic clearance.
authors.affiliation: Abbott Nutrition Research and Development, Singapore shreeram.sathya@abbott.com.
authors.forename: Sathyavageeswaran
authors.initials: S
authors.lastname: Shreeram
authors.affiliation: Abbott Nutrition Research and Development, Columbus, OH.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Johns
authors.affiliation: Abbott Nutrition Research and Development, Bangalore, India; and.
authors.forename: Swaminathan
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Syngene International Limited, Bangalore, India.
authors.forename: Subbarayan
authors.initials: S
authors.lastname: Ramesh
authors.affiliation: Syngene International Limited, Bangalore, India.
authors.forename: Vadakkanchery
authors.initials: V
authors.lastname: Vaidyanathan
authors.affiliation: Syngene International Limited, Bangalore, India.
authors.forename: Jithesh K
authors.initials: JK
authors.lastname: Puthan
authors.affiliation: Syngene International Limited, Bangalore, India.
authors.forename: Shibajee
authors.initials: S
authors.lastname: Mandal
authors.affiliation: Syngene International Limited, Bangalore, India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Mamidi
authors.affiliation: Abbott Nutrition Research and Development, Singapore.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gelling
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002118:Calcium / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019587:Dietary Supplements; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D014631:Valerates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005230:Fatty Acids, Nonesterified; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D002118:Calcium