Pharmacological differences between R(−)-and S(+)-ibuprofen
- 311 Downloads
Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug exhibiting optical isomerism. Only the racemate is in clincal use. Inin vitro studies it has been demonstrated that only the S(+)-enantiomer inhibits the PG synthetase system. Nevertheless, it is widely believed that the sole use of the active isomer does not comprise any advantages since the inactive isomer is converted within the human body. In a triple cross-over study (300 mg S(+), 300 mg R(−), 600 mg racemic IBU;n=8), we could show that the converted R(−)-IBU after racemate administration provides for only one third of the AUC of S(+)-IBU obtained after S(+)-application. Highest S(+)-peak plasma levels were reached after S(+)-IBU, lower ones after racemate. We, therefore, studied 4 patients with classical rheumatoid arthritis treated with 2–3 doses of 500 mg of S(+)-IBU/day over a two week period. Significant clinical recovery (Ritchie-indexp<0.01; analogue scale painp<0.05, motionp<0.01) was reached after one week. The results indicate that a reduction of dose and of metabolic load is possible if the S(+)-enantiomer is administrated.
KeywordsRheumatoid Arthritis Arthritis Ibuprofen Analogue Scale Peak Plasma
Unable to display preview. Download preview PDF.
- P. Jenner, B. Testa, Drug Metab. Rev.2, 117–184 (1974).Google Scholar
- S. S. Adams, P. Bresloff and C. G. Mason,Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of the (−)-isomer. J. Pharm. Pharmac.28, 256 (1976).Google Scholar
- K. Brune, U. Aehringhaus and B. A. Peskar,Pharmacological control of leukotriene and prostaglandin production from mouse peritoneal macrophages. Agents and Actions14, 729–734 (1984).Google Scholar
- K. Brune, K. D. Rainsford, K. Wagner and B. A. Peskar,Inhibition by anti-inflammatory drugs of prostaglandin production in cultured macrophages. Factors influencing the apparent drug effects. Naunyn-Schmiedebergs Arch. Pharmac.315, 269 (1981).Google Scholar
- G. Geisslinger, K. Dietzel, D. Loew, O. Schuster, G. Rau, G. Lachmann and K. Brune,High performance liquid chromatographic determination of ibuprofen, its metabolites and enantiomers in biological fluids. J. Chromato. (in press, 1989).Google Scholar
- G. Heinzel,TOPFIT InDrug development and evaluation, vol. 6 (Eds. G. Bozler and J. M. van Rossum). Fischer Verlag, Stuttgart, New York 1982.Google Scholar