Clinical Drug Investigation

, Volume 14, Issue 6, pp 474–481

Parenteral versus Oral Route Increases Paracetamol Efficacy

  • O. Jarde
  • E. Boccard
Clinical Use

Summary

The analgesic efficacy and tolerability of parenteral versus oral paracetamol 1g were compared in 323 patients immediately after a hallux valgus plasty performed with local anaesthesia (31 men, 292 women, mean age 52 years). Using a multicentre, double-blind, double-placebo, randomised, parallel-group design, the effects of a single dose of propacetamol (PR) 2g [= paracetamol (PA) 1g], oral PA 1g and placebo (PL) were compared in the recovery room 5 hours (mean) after surgery in three parallel groups of patients with at least moderate pain on a 5-point verbal scale. Efficacy was assessed on pain scores rated on a 5-point verbal scale before administration (T0) and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5 and 6 hours after administration and with an overall efficacy 5-point verbal score. Any adverse effects were recorded throughout the duration of the study. PR was statistically superior to PL on pain intensity difference (PID) from T30 minutes to T6 hours (Dunnett test), on maximum pain intensity difference (MAXPID) [p < 0.05] and summed pain intensity difference (SPID) [p < 0.05]. PA was statistically superior to PL at T1, T2, T4, T5 hours (Dunnett test), on MAXPID (p < 0.05) and SPID (p < 0.10). PR was statistically superior to PA on PID from T30 minutes to T4 hours, on MAXPID (p < 0.03) and SPID (p < 0.01). Overall efficacy was found by the patients to be superior with PR vs PA (p < 0.01), PR vs PL (p < 0.05), and PA vs PL (p < 0.10). The remedication time was significantly different between the three groups (p < 0.05). 10 patients experienced 1 adverse effect, PR: 3 (injection site pain, headache, vomiting), PA: 6 [nausea, tremor, injection site pain (3), malaise], PL: 1 (injection site pain). In conclusion, PR 2g (i.e. PA 1g) provided a significantly greater and longer analgesic effect than the same dosage in oral form.

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References

  1. 1.
    Lechat P, Kirsch R. Le paracétamol, actualisation des connaissances en 1989. Thérapie 1989; 44: 337–54PubMedGoogle Scholar
  2. 2.
    Ivey KJ. Gastrointestinal effects of antipyretic analgesics. Am J Med 1983; 1: 53–64CrossRefGoogle Scholar
  3. 3.
    Mielke CH. Comparative effects of aspirin and paracetamol on hemostasis. Arch Intern Med 1981; 141: 305–10PubMedCrossRefGoogle Scholar
  4. 4.
    Delacroix P, Kenesi C, Stoppa R. Evaluation de l’efficacité antalgique du propacétamol versus placebo chez des patients présentant une douleur post-opératoire. Sem Hop Paris 1985; 61: 2739–42Google Scholar
  5. 5.
    De Marneffe R, Mokassa L. Etude comparative de l’activité antalgique du propacétamol et d’une aspirine injectable, l’acetylsalicylate de lysine: compte-rendus de thérapeutique et de pharmacologie clinique. Compte-redus Ther Pharm Clin 1985; 29: 23–7Google Scholar
  6. 6.
    Ang ET, Goldfarb G, Boccard E. Analgesic efficacy of propacetamol hydrochloride 2g versus pentazocine 30mg after orthopedic surgery. Eur J Pain 1990; 11: 137–42Google Scholar
  7. 7.
    Van Acken H, Gerin M, Thijs J, et al. Comparative analgesic efficacy of repeated dosing of propacetamol and morphine on postoperative pain after oral surgery. VIII World Congress on Pain, Vancouver, 1996: 265Google Scholar
  8. 8.
    Hynes D, McCarroll M, Gerin M, et al. Propacetamol vs diclofenac and placebo for post-operative pain control after hip arthroplasty. VIII World Congress on Pain, Vancouver, 1996: 266Google Scholar
  9. 9.
    Bannwarth B, Netter P, Lapicque F, et al. Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. Br J Clin Pharmacol 1992; 34: 79–81PubMedCrossRefGoogle Scholar
  10. 10.
    Piletta P, Porchet HC, Dayer P. Central analgesic effect of paracetamol but not aspirin. Clin Pharmacol Ther 1991; 49: 350–4PubMedCrossRefGoogle Scholar
  11. 11.
    Granry JC, Rod B, Boccard E, et al. Pharmacokinetics and antipyretic effects of an injectable pro-drug of paracetamol (propacetamol) in children. Pediatr Anesth 1992; 2: 291–5CrossRefGoogle Scholar
  12. 12.
    Rod B, Monrigal JP, Lepoittevin L, et al. Traitement de la douleur postopératoire chez l’enfant en salle de réveil. Cah Anesthesiol 1989; 37: 525–30PubMedGoogle Scholar
  13. 13.
    Marichy J, Bouchard C, Nombret T, et al. Efficacité antipyrétique du propacétamol chez des enfants brûlés graves. Cah Anesthesiol 1989; 37: 521–3PubMedGoogle Scholar
  14. 14.
    Granry JC, Rod B, Boccard E, et al. The analgesic efficacy of an injectable produg of paracetamol in children at 30 mg/kg after limb orthopedic surgery. Pediatr Anesth. In pressGoogle Scholar
  15. 15.
    Hans P, Brichaut JF, Bonhomme V, et al. Analgesic efficiency of propacetamol hydrochloride after lumbar disc surgery. Acta Anaesth Belg 1993; 44: 129–33PubMedGoogle Scholar
  16. 16.
    Farkas JC, Larrouturou P, Morin JP, et al. Analgesic efficacy of an injectable paracetamol versus a dipyrone plus pitofenone plus fenpiverinium association after abdominal aortic repair. Curr Ther Res 1991; 51: 19–27Google Scholar
  17. 17.
    Lobera A, Lakdja F, Faucher A, et al. Place du propacétamol dans l’analgésie prophylactique postopératoire: à propos de cent-vingt observations. Sem Hop 1991; 67: 1170–94Google Scholar
  18. 18.
    Garrec F, Chupin AM, Souron R. Analgésie post-opératoire par le propacétamol. Cah Anesthesiol 1991; 39: 333–5PubMedGoogle Scholar
  19. 19.
    Moreau X, Cottineau C, Cocaud J, et al. Analgésie postopératoire en chirurgie veineuse périphérique. Cah Anesthesiol 1990; 38: 403–4PubMedGoogle Scholar
  20. 20.
    Depre M, van Hecken A, Verbesselt R, et al. Tolerance and pharmacokinetics of propacetamol, a paracetamol formulation for intravenous use. Fundam Clin Pharmacol 1992; 6: 259–62PubMedCrossRefGoogle Scholar
  21. 21.
    Farhat F, Savoyen MC, Jayr C. Efficacité du propacétamol sur la douleur post-opératoire selon deux modes d’administration intraveineuse. Cah Anesthésiol 1995; 4: 351–6Google Scholar
  22. 22.
    Tauzin P, Delort-Laval S, Guenard Y, et al. Etude comparative de la buprénorphine et de son association au Kétoprophéne et au propacétamol pour l’analgésie postopératoire en chirurgie urologique. Ann Fr Anesth Réanim 1996; 15: 41–6CrossRefGoogle Scholar
  23. 23.
    Hans P, Brichant JF, Bonhomme V, et al. Analgesic efficiency of propacetamol hydrochloride after lumbar disc surgery. Acta Anesthesiol Belg 1993; 44(4): 129–33Google Scholar
  24. 24.
    Luthy CS, Collart L, Dayer P. The rate of administration influences the analgesic effect of paracetamol. Clin Pharm Ther 1993; 2: 171Google Scholar
  25. 25.
    Piguet V, Desmeubles J, Collart L, et al. Lack of paracetamol ceiling effect on RIII nociceptive flexion reflex. Clin Pharm Ther 1994; 55: 124Google Scholar
  26. 26.
    Skoglund LA, Skjelbred P, Fyllingen G. Analgesic efficacy of acetaminophen 1000mg, acetaminophen 2000mg, and the combination of acetaminophen 1000mg and codeine phosphate 60mg versus placebo in acute postoperative pain. Pharmacotherapy 1991; 11(5): 364–9PubMedGoogle Scholar
  27. 27.
    Regnauld B. Le pied. Berlin: Springer Verlag, 1986: 274–320Google Scholar
  28. 28.
    Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81CrossRefGoogle Scholar
  29. 29.
    Benedetti C, Bonia JJ, Belluci G. Pathophysiology and therapy of post-operative pain: a review. In: Advances in pain research and therapy. Vol. 7. New York: Raven Press, 373–407Google Scholar
  30. 30.
    Peirce RJ, Fragen RJ, Pemberton DM. Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate operative pain. Pharmacotherapy 1990; 10: 111SPubMedGoogle Scholar
  31. 31.
    Brown CR, Moodie JE, Wild VM, et al. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy 1990; 10: 116SPubMedGoogle Scholar
  32. 32.
    Delbos A, Boccard E. The morphine-sparing effect of pro-pacetamol in orthopedic postoperative pain. J Pain Symptom Manage 1995; 10(4): 279–86PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  • O. Jarde
    • 1
  • E. Boccard
    • 2
  1. 1.Orthopaedic Surgery DepartmentHôpital NordAmiensFrance
  2. 2.Laboratoires UPSARueil-Malmaison CédexFrance

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