Enantioselective disposition of clenbuterol in rats

Biopharm Drug Dispos. 2014 May;35(4):207-17. doi: 10.1002/bdd.1885. Epub 2013 Dec 26.


Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1 ml volumes of plasma were precisely quantified at concentrations as low as 0.25 ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2 mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17 l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14 l/kg). The total body clearance of (-)-R-clenbuterol (13.5 ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5 ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding.

Keywords: clenbuterol; enantiomer; excretion; pharmacokinetics; protein binding.

MeSH terms

  • Adrenergic beta-Agonists / blood
  • Adrenergic beta-Agonists / chemistry*
  • Adrenergic beta-Agonists / pharmacokinetics*
  • Adrenergic beta-Agonists / urine
  • Animals
  • Bile / chemistry
  • Blood Proteins / metabolism
  • Clenbuterol / blood
  • Clenbuterol / chemistry*
  • Clenbuterol / pharmacokinetics*
  • Clenbuterol / urine
  • Male
  • Protein Binding
  • Rats, Wistar
  • Stereoisomerism
  • Tissue Distribution


  • Adrenergic beta-Agonists
  • Blood Proteins
  • Clenbuterol