YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Physicochemical Characteristics and Pharmacokintics of Ibuprofen Lysine Salts

흰쥐에서 이부프로펜 리신염의 물리화학적 특성 및 약물동태에 관한 평가

  • Shin, Dae-Hwan (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Kim, Tai-Sung (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Park, Seong-Hyeok (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Kim, Si-Hyun (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Jo, Han-Jun (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Han, Kun (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Chung, Youn-Bok (CBITRC, College of Pharmacy, Chungbuk National University)
  • Received : 2011.05.13
  • Accepted : 2011.06.08
  • Published : 2011.06.30
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Abstract

Two types of water soluble lysine salts of ibuprofen were prepared and evaluated. Physicochemical properties for ibuprofen-l-lysinate (IBL-l), ibuprofen-dl-lysinate (IBL-dl) and ibuprofen (IB) were studied on melting point, specific ratation, UV spectra and $^1H$-NMR spectra. There were not differences between IBL-dl and IBL-l in UV spectra and $^1H$-NMR spectra. The pharmacokinetic parameters of IB were compared to those of its lysine salts (IBL-l and IBL-dl) after i.v. or oral administration at the dose of 50 mg/kg (calculated as IB). Total body clearance ($CL_t$) and area under the plasma concentration-time curve (AUC) were not different between IB group and IBL groups after i.v. administration. On the other hand, IBL-l and IBL-dl produced peak plasma concentrations ($C_{max}$) significantly ealier and higher than IB. Time to reach peak concentration ($T_{max}$) after IBL administration was lower than that after IB administration. There was no difference in AUC across all different groups (IB, IBL-l and IBL-dl) after oral administration. However, absorption rate constant ($k_a$) of IBL-l and IBL-dl were significantly increased than that of IB. These results indicated that the administration of IBL-l and IBL-dl may be advantageous if rapid and reliable onset of pain relief is required.

Keywords

References

  1. Luckow, V., Krammer, R. and Traub, R. : Comparative biological availability of two different ibuprofen granules. Arzneimittelforschung. 42, 1339 (1992).
  2. Hermann, T. and Glowka, F. K. : Biological availability of ibuprofen in Imbun 500 suppositories. Acta. Pol. Pharm. 47, 37 (1990).
  3. Geisslinger, G., Dietzel, K. and Bezler, H. : Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int. J. Clin. Pharmacol. Ther. Toxicol. 27, 324 (1989).
  4. Hermann, T. W., Gtowka, F. K. and Garrett, E. R. : Bioavailability of racemic ibuprofen and its lysinate from suppositories in rabbits. J. Pharm. Sci. 82, 1102 (1993). https://doi.org/10.1002/jps.2600821108
  5. Bookstaver, P. B., Miller, A. D. and Rudisill, C. N. : Intravenous ibuprofen : the first injectable product for the treatment of pain and fever. J. Pain. Res. 3, 67 (2010).
  6. Ambat, M. T., Ostrea, E. M., Jr. and Aranda, J. V. : Effect of ibuprofen L-lysinate on bilirubin binding to albumin as measured by saturation index and horseradish peroxidase assays. J. Perinatol. 28, 287 (2008). https://doi.org/10.1038/sj.jp.7211925
  7. Glowka, F. K. : Stereoselective pharmacokinetics of ibuprofen and its lysinate from suppositories in rabbits. Int. J. Pharm. 199, 159 (2000). https://doi.org/10.1016/S0378-5173(00)00377-X
  8. Ehnhage, A., Kolbeck, K. G. and Juto, J. E. : Evaluation of nasal mucosal swelling and microcirculation throughout nasal and bronchial provocation tests with lysine-aspirin in asthmatics with nasal polyposis. Rhinology 48, 216 (2010).
  9. Marzo, A., Reiner, A. and Arrigoni Martelli, E. : Bioavailability of indomethacin from a modified release system containing indomethacin as the lysine salt. Eur. J. Clin. Pharmacol. 32, 85 (1987). https://doi.org/10.1007/BF00609963
  10. Segre, E. J. : Letter : Ibuprofen therapy. Arthritis Rheum. 18, 628 (1975).
  11. Ariens, E. J. : Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology. Eur. J. Clin. Pharmacol. 26, 663 (1984). https://doi.org/10.1007/BF00541922
  12. Jozwiak, K., Toll, L. and Jimenez, L. : The effect of stereochemistry on the thermodynamic characteristics of the binding of fenoterol stereoisomers to the beta(2)-adrenoceptor. Biochem. Pharmacol. 79, 1610 (2010). https://doi.org/10.1016/j.bcp.2010.01.035
  13. Vogensen, S. B., Greenwood, J. R. and Bunch, L. : Glutamate receptor agonists : stereochemical aspects. Curr. Top. Med. Chem. 11, 887 (2011). https://doi.org/10.2174/156802611795164990
  14. Wade, D. N., Mearrick, P. T. and Morris, J. L. : Active transport of L-dopa in the intestine. Nature 242, 463 (1973). https://doi.org/10.1038/242463a0
  15. Contin, M. and Martinelli, P. : Pharmacokinetics of levodopa. J. Neurol. 257, 253 (2010).
  16. Cook, C. E., Seltzman, T. B. and Tallent, C. R. : Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits. J. Pharmacol. Exp. Ther. 241, 779 (1987).
  17. Filippi, L., la Marca, G. and Cavallaro, G. : Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy : A pharmacokinetic study during whole body hypothermia. Epilepsia 52, 794 (2011). https://doi.org/10.1111/j.1528-1167.2011.02978.x
  18. Mc, M. R. and Oncley, J. L. : The specific binding of Ltryptophan to serum albumin. J. Biol. Chem. 233, 1436 (1958).
  19. Schmidt, W. and Jahnchen, E. : Species-dependent stereospecific serum protein binding of the oral anticoagulant drug phenprocoumon. Experientia 34, 1323 (1978). https://doi.org/10.1007/BF01981447
  20. Imamura, Y., Mori, H. and Otagiri, M. : Differential effects of ketoprofen on the pharmacokinetics of sulphadimethoxine in fast and slow acetylator rabbits. J. Pharm. Pharmacol. 42, 62 (1990). https://doi.org/10.1111/j.2042-7158.1990.tb05353.x
  21. Sakai, T., Maruyama, T. and Imamura, H. : Mechanism of stereoselective serum binding of ketoprofen after hemodialysis. J. Pharmacol. Exp. Ther. 278, 786 (1996).