Drug Res (Stuttg) 2013; 63(01): 34-37
DOI: 10.1055/s-0032-1331693
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Enantioselective Disposition after Single Dose I.V Administration of Ketorolac in Male Wistar Rats

S. K. Dubey
1   Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India
,
R. N. Saha
1   Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India
,
N. Mittapelly
1   Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India
,
A. Anand
1   Department of Pharmacy, Birla Institute of Technology & Science, Pilani, India
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 30. September 2012

accepted 20. November 2012

Publikationsdatum:
08. Januar 2013 (online)

Abstract

Ketorolac, a commonly used anti-inflamatory and analgesic agent, was studied in male wistar rats. The plasma samples were analysed using chiral AGP column with UV detection. The experimental data was analysed for probable fit in the compartmental and non-compartmental models using WinNolin software. The data of (+)-R-Ketorolac and (−)-S-Ketorolac was found to fit into the compartmental as well as non compartmental model. There was a difference between the plasma concentrations of (+)-R-Ketorolac and (−)-S-Ketorolac; the plasma concentrations of (+)-R-Ketorolac were higher than those of (−)-S-Ketorolac throughout the time course of the study. The area under the curve (AUC) of time vs. concentration profile of (+)-R-Ketorolac was found to be higher than (−)-S-Ketorolac. Volume of distribution and clearance was found to be higher for (−)-S-Ketorolac.

 
  • References

  • 1 Rooks WH, Maloney PJ, Shott LD et al. The analgesic and anti-inflammatory profile of Ketorolac and its tromethamine salt. Drugs Exp Clin Res 1985; 11: 479-492
  • 2 Pallapies D, Salinger A, Meyer Zum Gottesberge et al. Effects of lysine clonixinate and Ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo. Life Sci 1995; 57: 83-89
  • 3 Galan-Herrera JF, Poo JL, Maya-Barrios JA et al. Bioavailability of two sublingual formulations of Ketorolac tromethamine 30 mg: A randomized, open-label, single-dose, two-period crossover comparison in healthy Mexican adult volunteers. Clin Ther 2008; 30: 1667-1674
  • 4 Zhang Y, Shaffer A, Portanova J et al. Inhibition of cyclooxygenase-2 rapidly reverses inflammatory hyperalgesia and prostaglandin E2 production. J Pharmacol Exp Ther 1997; 283: 1069-1075
  • 5 Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors and lessons from the clinic. FASEB J 2004; 18: 790-804
  • 6 Guzman A, Yuste F, Toscana RA et al. Absolute configuration of (-)-5-benzoyl-1, 2-dihydro-3H-pyrrolo [1, 2-alpha] pyrrole-1-carboxylic acid, the active enantiomer of Ketorolac. J Med Chem 1986; 29: 589-591
  • 7 Nagilla R, Deshmukh DD, Copedge KJ et al. The pharmacokinetics of ketorolac enantiomers following intramuscular administration of the racemate. J Vet Pharmacol Ther 2009; 32: 49-55
  • 8 Jung D, Mroszczak E, Bynum L. Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration. Eur J Clin Pharmacol 1988; 35: 423-425
  • 9 Mindy NC, Uwe C, Thomas H et al. Pharmacokinetics of Single-Dose Intravenous Ketorolac in Infants Aged 2–11 Months. Anesth Analg 2011; 112: 655-660
  • 10 Anne ML, Heidi B, Eric D et al. Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months. Paediatr Anaesth 2011; 21: 325-334
  • 11 Kauffman RE, Lieh-Lai MW, Uy HG et al. Enantiomer-selective pharmacokinetics and metabolism of ketorolac in children. Clin Pharmacol Ther 1999; 65: 382-388
  • 12 Hamunen K, Maunuksela EL, Sarvela J et al. Stereoselective pharmacokinetics of ketorolac in children, adolescents and adults. Acta Anaesthesiol Scand 1999; 43: 1041-1046
  • 13 Hayball J, Wrobel J, Tamblyn JG et al. The pharmacokinetics of ketorolac enantiomers following intramuscular administration of the racemate. Br J clin Pharmac 1994; 37: 75-78
  • 14 Drover DR, Hammer GB, Anderson BJ. The pharmacokinetics of ketorolac after single postoperative intranasal administration in adolescent patients. Anesth Analg 2012; 114: 1270-1276
  • 15 Pasloske K, Renaud R, Burger J et al. Pharmacokinetics of ketorolac after intravenous and oral single dose administration in dogs. J Vet Pharmacol Ther 1999; 22: 314-319
  • 16 Jamali F, Lovlin R, Corrigan BW et al. Stereospecific pharmacokinetics and toxicodynamics of ketorolac after oral administration of the racemate and optically pure enantiomers to the rat. Chirality 1999; 11: 201-205
  • 17 Nagilla R, Deshmukh DD, Duran SH. Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose. J Vet Pharmacol Ther 2007; 30: 437-442
  • 18 Wang M, Liu W, Lu Q. Pharmacokinetic comparison of ketorolac after intracameral, intravitreal, and suprachoroidal administration in rabbits. Neurosurgery. 2012
  • 19 Nagilla R, Deshmukh DD, Copedge KJ et al. Enantiomeric disposition of ketorolac in goats following administration of a single intravenous and oral dose. J Vet Pharmacol Ther 2009; 32: 49-55
  • 20 Santos Ballesteros Ros et al. Chiral pharmacokinetics of ketorolac in sheep after intravenous and intramuscular administration of the racemate. J Vet Pharmacol Ther 2001; 24: 443-446
  • 21 Dipanjan G, Ajay K, Sunil KD et al. Liquid Chromatographic tandem mass spectrometric validated method for pharmacokinetic estimation of flecainide in human plasma. Clin Res Regul Aff 2009; 26: 24-36