Summary
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 (Vdβ) 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.
Similar content being viewed by others
References
Lindén I-B, Parantainen J, Vapaatalo H (1976) Inhibition of prostaglandin biosynthesis by tolfenamic acid in vitro. Scand J Rheum 5: 129–132
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 287–300
Kajander A, Martio J, Mutru O, Gothoni G (1976) Prolonged treatment with tolfenamic acid in inflammatory rheumatic diseases. Scand J Rheum 4: 158–160
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: 13–16
Kauppila A, Ylikorkala O (1977) Indomethacin and tolfenamic acid in primary dysmenorrhea. Eur J Obstet Gynecol Reprod Biol 7: 59–64
Hakkarainen H, Vapaatalo H, Gothoni G, Parantainen J (1979) Tolfenamic acid is as effective as ergotamine during migraine attacks. Lancet 2: 326–328
A/S GEA (1977) Clotam® information bulletin. Richard Larsen a-s, Copenhagen
Glazko AJ (1967) Pharmacology of the fenemates. III. Metabolic disposition. Ann Phys Med 9: 23–36
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: 189–193
Sedman AJ, Wagner JG (1974) AUTOAN, a decision-making pharmacokinetic computer programm. Distributed by Publication Service, 615 East university avenue, Ann Arbor, MI 46106, USA
Metzler CM, Elfring GL, McEven AJ (1974) A package of computer programs for pharmacokinetic modeling. Biometrics 30: 562
Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i. v. infusion. J Pharm Sci 59: 53–55
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: 117–123
Loo JCK, Riegelman S (1968) New method for calculating the intrinsic absorption rate of drugs. J Pharm Sci 57: 918–928
Von Dell H-D, Fiedler J, Jacobi H, Wäsche B (1977) Zur Biochemie und Pharmakokinetic von Etofenamat. Arzneim Forsch 27: 1322–1325
Adamska-Dyniewska H, Kowakzyk L, Tkaczewski W (1979) Farmakokinetyka kwasu mefenaminowego u chorych z przewlekla niewydolnościa krażenia. Pol Tyg Lek 34: 177–180
Tamassia V, Corvi G, Moro E, Tosolini GP, Fucella LM (1976) Pharmacokinetics and bioavailability of indoprofen in man. Eur J Clin Pharmacol 10: 257–262
Caillé G, Besner J-G, Brodeur J, Vezina M (1978) Profil pharmacocinétique du kétoprofène. Ann Pharm Fr 36: 243–252
Brogden RN, Pinder RM, Speight TM, Avery GS (1977) Fenoprofen: A review of its pharmacological properties and therapeutic efficay in rheumatic diseases. Drugs 13: 241–265
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: 405–410
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: 241–277
Pentikäinen PJ, Neuvonen PJ, Penttilä A, Backman C (1980) Pharmacokinetics of tolfenamic acid. Abstracts, World Conference on Clinical Pharmacology and Therapeutics, London
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pentikäinen, P.J., Neuvonen, P.J. & Backman, C. Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent. Eur J Clin Pharmacol 19, 359–365 (1981). https://doi.org/10.1007/BF00544587
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00544587