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The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen

Summary

A 250 mg tablet of timegadine was given twice daily for 15 days to 13 healthy volunteers. On Day 16 a single morning dose of timegadine was supplemented by two 200 mg tablets of a proprietary brand of ibuprofen.

Serum concentrations of timegadine were measured by high pressure liquid chromatography, and steady state was achieved between Days 5 and 8. Serum concentrations of two metabolites of time-gadine, MI and MII were measured by thin layer chromatography by Leo Pharmaceutical Products, Denmark.

Ibuprofen did not significantly affect the serum half-time of timegadine, but did reduce the maximum measured serum timegadine concentration, the area under the serum concentration versus time curve and the time to achieve maximum measured serum concentration.

Serum liver enzymes remained within the normal ranges and there were no changes in hepatic microsomal enzyme activity as assessed by urinary excretion ofD-glucaric acid.

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References

  1. Ahnfelt-Ronne I, Arrigoni-Martelli E (1980) A new anti-inflammatory compound timegadine which inhibits both prostaglandin and 12-hydroxyeicosatatraenoic acid (12-HETE) formation. Biochem Pharmac 29: 3265–3269

  2. Colombi A, Marioni M, Antonini C, Cassina T, Gambini A, Foa V (1983) Low pH method for the enzymatic assay ofD-glucaric acid in urine. Clin Chim Acta 128: 337–347

  3. Craig GL, Buchanan WW (1980) Antirheumatic drugs: Clinical pharmacology and therapeutic use. Drugs 20: 453–484

  4. Ekstrand R, Alvan G, Borga O (1979) Concentration dependent plasma protein binding of salicylate in rheumatoid patients. Clin Pharmacokinet 4: 137–143

  5. Emori HW, Paulus H, Bluestone R, Champion GD, Pearson C (1976) Indomethacin serum concentrations in man: Effects of dosage, food and antacid. Ann Rheum Dis 35: 333–338

  6. Fourtillan JB, Courtois P, Lefebvre MA, Girault J (1981) Pharmacokinetics of oral timolol studied by mass fragmentography. Eur J Clin Pharmacol 19: 193–196

  7. George S, Dauwe K, McBurney A, Ward J (1983) The influence of food intake on the bioavailability of timegadine, a novel non-steroidal anti-inflammatory drug. Br J Clin Pharmacol 15: 495–498

  8. George S, McBurney A, Ward J (1984) The protein binding of timegadine determined by equilibrium dialysis. Br J Clin Pharmacol 18: 785–790

  9. Gibaldi M, Perrier D (1982) Chapter 3. Multiple dosing. In: Pharmacokinetics, 2nd edn Marcel Dekker, New York

  10. Goldberg DM (1980) The expanding role of microsomal enzyme induction, and its implications for clinical chemistry. Clin Chem 26: 691–699

  11. Grennan DM, Aarons L, Siddiqui M, Richards M, Thompson R, Higham C (1983) Dose-response study with ibuprofen in rheumatoid arthritis: Clinical and pharmacokinetic findings. Br J Clin Pharmacol 15: 311–316

  12. Hildebrandt AG, Roots I, Speck M, Saalfrank K, Kewitz H (1975) Evaluation of in vivo parameters of drug metabolising activity in man after administration of clemastine, phenobarbital or placebo. Eur J Clin Pharmacol 8: 327–336

  13. Hobbs DC (1983) Pharmacokinetics of piroxicam in man. Eur J Rheumatol Inflamm 6: 46–55

  14. Houston JB, Taylor G (1984) Drug metabolite concentration-time profiles: Influence of route of drug administration. Br J Clin Pharmacol 17: 385–394

  15. Mandelli M, Tognoni G (1980) Monitoring plasma concentrations of salicylate. Clin Pharmacokinet 5: 424–440

  16. Park BK (1982) Assessment of the drug metabolism capacity of the liver. Br J Clin Pharmacol 14: 631–651

  17. Taggart HMcA, Alderdice JM (1982) Fatal cholestatic jaundice in elderly patients taking benoxaprofen. Br Med J 284: 1372

  18. Tilstone WJ, Lawson DH, Omara F, Cunningham F (1981) The steady state pharmacokinetics of piroxicam: Effect of food and iron. Eur J Rheumatol Inflamm 4: 309–313

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George, S., McBurney, A. & Ward, J.W. The pharmacokinetics of timegadine and two of its metabolites after multiple oral dosing, and the effects of concomitant administration of ibuprofen. Eur J Clin Pharmacol 29, 581–586 (1986). https://doi.org/10.1007/BF00635896

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Key words

  • timegadine
  • ibuprofen
  • anti-inflammatory
  • pharmacokinetics
  • enzyme induction