European Journal of Clinical Pharmacology

, Volume 19, Issue 5, pp 359–365 | Cite as

Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent

  • P. J. Pentikäinen
  • P. J. Neuvonen
  • C. Backman


The pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent was studied in six healthy volunteers after an intravenous dose of 100 mg and oral doses of 100, 200, 400 and 800 mg. The disposition of intravenous tolfenamic acid could be described by two-compartment open model, with a central compartment volume (Vdc) of 5.6±0.31 (mean±SE), volume during β-phase (V) of 31±21, and a total elimination rate constant (k10) 1.6±0.1 h−1. The terminal elimination half-life was 2.5±0.6 h and the total plasma clearance 155±15 ml/min. The elimination occured principally by extrarenal mechanisms, the recovery of unchanged drug together with is glucuronide in urine averaging only 8.8% of the intravenous dose. The binding of tolfenamic acid to plasma proteins averaged 99.7%. The gastrointestinal absorption had a mean half-life of 1.7±0.1 h. Based on comparison of areas under the plasma concentration time-curves after intravenous and oral administration, the biovailability of tolfenamic acid capsules averaged 60%. The rate and extent of absorption and the rate of elimination of tolfenamic acid were independent of dose.

Key words

tolfenamic acid anti-inflammatory agent human pharmacokinetics bioavailability intravenous administration 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lindén I-B, Parantainen J, Vapaatalo H (1976) Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro. Scand J Rheum 5: 129–132Google Scholar
  2. 2.
    Vapaatalo H, Parantainen J, Lindén I-B, Hakkarainen H (1977) Prostaglandins and vascular headache; action of tolfenamic acid, a new anti-inflammatory analgetic, on migraine. Proceedings of the joint meeting of the Italian and the Scandinavien Migraine societes. “Headache: New Vistas”. Biomedical Press, Florence, pp 287–300Google Scholar
  3. 3.
    Kajander A, Martio J, Mutru O, Gothoni G (1976) Prolonged treatment with tolfenamic acid in inflammatory rheumatic diseases. Scand J Rheum 4: 158–160Google Scholar
  4. 4.
    Rejholec V, Vapaatalo H, Tokola O, Gothoni G (1979) A comparative, double-blind study on tolfenamic acid in the treatment of rheumatoid arthritis. Scand J Rheum (Suppl) 24: 13–16Google Scholar
  5. 5.
    Kauppila A, Ylikorkala O (1977) Indomethacin and tolfenamic acid in primary dysmenorrhea. Eur J Obstet Gynecol Reprod Biol 7: 59–64Google Scholar
  6. 6.
    Hakkarainen H, Vapaatalo H, Gothoni G, Parantainen J (1979) Tolfenamic acid is as effective as ergotamine during migraine attacks. Lancet 2: 326–328Google Scholar
  7. 7.
    A/S GEA (1977) Clotam® information bulletin. Richard Larsen a-s, CopenhagenGoogle Scholar
  8. 8.
    Glazko AJ (1967) Pharmacology of the fenemates. III. Metabolic disposition. Ann Phys Med 9: 23–36Google Scholar
  9. 9.
    Ehrnebo M, Agurell S, Jalling B, Boréus LO (1971) Age differences in drug binding by plasma proteins: Studies on human foetus, neonates and adults. Eur J Clin Pharmacol 3: 189–193Google Scholar
  10. 10.
    Sedman AJ, Wagner JG (1974) AUTOAN, a decision-making pharmacokinetic computer programm. Distributed by Publication Service, 615 East university avenue, Ann Arbor, MI 46106, USAGoogle Scholar
  11. 11.
    Metzler CM, Elfring GL, McEven AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30: 562Google Scholar
  12. 12.
    Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i. v. infusion. J Pharm Sci 59: 53–55Google Scholar
  13. 13.
    Riegelman S, Loo JCK, Rowland M (1968) Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J Pharm Sci 57: 117–123Google Scholar
  14. 14.
    Loo JCK, Riegelman S (1968) New method for calculating the intrinsic absorption rate of drugs. J Pharm Sci 57: 918–928Google Scholar
  15. 15.
    Von Dell H-D, Fiedler J, Jacobi H, Wäsche B (1977) Zur Biochemie und Pharmakokinetic von Etofenamat. Arzneim Forsch 27: 1322–1325Google Scholar
  16. 16.
    Adamska-Dyniewska H, Kowakzyk L, Tkaczewski W (1979) Farmakokinetyka kwasu mefenaminowego u chorych z przewlekla niewydolnościa krażenia. Pol Tyg Lek 34: 177–180Google Scholar
  17. 17.
    Tamassia V, Corvi G, Moro E, Tosolini GP, Fucella LM (1976) Pharmacokinetics and bioavailability of indoprofen in man. Eur J Clin Pharmacol 10: 257–262Google Scholar
  18. 18.
    Caillé G, Besner J-G, Brodeur J, Vezina M (1978) Profil pharmacocinétique du kétoprofène. Ann Pharm Fr 36: 243–252Google Scholar
  19. 19.
    Brogden RN, Pinder RM, Speight TM, Avery GS (1977) Fenoprofen: A review of its pharmacological properties and therapeutic efficay in rheumatic diseases. Drugs 13: 241–265Google Scholar
  20. 20.
    Willis JV, Kendall MJ, Flinn RM, Thornhill DP, Welling PG (1979) The pharmacokinetics of diclofenac sodium following intravenous and oral administration. Eur J Clin Pharmacol 16: 405–410Google Scholar
  21. 21.
    Brogden RN, Heel RC, Speight TM, Avery GS (1979) Naproxen up to date: A review of its pharmacological properties and therapeutic efficacy and use in rheumatic diseases and pain states. Drugs 18: 241–277Google Scholar
  22. 22.
    Pentikäinen PJ, Neuvonen PJ, Penttilä A, Backman C (1980) Pharmacokinetics of tolfenamic acid. Abstracts, World Conference on Clinical Pharmacology and Therapeutics, LondonGoogle Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • P. J. Pentikäinen
    • 1
  • P. J. Neuvonen
    • 2
  • C. Backman
    • 3
  1. 1.Department of MedicineUniversity of KuopioFinland
  2. 2.Department of Clinical PharmacologyUniversity of HelsinkiHelsinkiFinland
  3. 3.Research Laboratories of Medica Pharmaceutical Company Ltd.HelsinkiFinland

Personalised recommendations