Clinical Pharmacokinetics

, Volume 42, Issue 4, pp 373–379 | Cite as

Pharmacokinetics of Intravenous and Rectal Ketoprofen in Young Children

Original Research Article

Abstract

Objective: To evaluate the relative bioavailabilities of ketoprofen after intravenous and rectal administration to young children.

Design: Open-label prospective parallel-group study.

Patients: Participants were 28 children aged 7 to 93 months.

Methods: Eighteen children received a single intravenous injection of ketoprofen 1 mg/kg, and ten children, weight 16–24 kg, received a 25mg ketoprofen suppository. Venous blood samples were collected at selected times after administration, ranging from 2 minutes to 8 hours for the intravenous group and from 30 minutes to 8 hours for the suppository group. A validated high performance liquid chromatography method was used to measure plasma ketoprofen concentrations.

Results: In the intravenous group, the maximum plasma concentration of ketoprofen ranged between 10.5 and 22.2 mg/L, and in the suppository group, following dose normalisation to 1 mg/kg of ketoprofen, between 3.8 and 7.4 mg/L. In the intravenous group, area under the concentration-time curve from zero to infinity ranged between 9.2 and 23.5 mg · h/L, and in the suppository group after dose normalisation between 8.8 and 12.9 mg · h/L. The bioavailability of ketoprofen from the suppository was about 73%. Volume of distribution was 0.04–0.10 L/kg in the intravenous group and 0.08–0.16 L/kg in the suppository group. The terminal half-life was comparable in both study groups, ranging between 0.7 and 3.0 hours in the intravenous group and between 1.2 and 2.9 hours in the suppository group.

Conclusion: Absorption of ketoprofen after rectal administration is reasonably rapid and predictable. Because the bioavailability of rectal ketoprofen is also relatively high, a suppository may be used in children in whom the drug cannot be given intravenously or by mouth.

References

  1. 1.
    Schirm E, van den Berg P, Gebben H, et al. Drug use of children in the community assessed through pharmacy dispensing data. Br J Clin Pharmacol 2000; 50: 473–8PubMedCrossRefGoogle Scholar
  2. 2.
    Fossgreen J. Ketoprofen: a survey of current publications. Scand J Rheumatol 1976; 14: 7–32Google Scholar
  3. 3.
    Keinänen-Kiukaanniemi S, Similä S, Kouvalainen K. Oral antipyretic therapy evaluation of the propionic acid derivates, ibuprofen, ketoprofen, fenoprofen and naproxen. Padiatr Padol 1980; 15: 239–44Google Scholar
  4. 4.
    Kantor TG. Ketoprofen: a review of its pharmacologic and clinical properties. Pharmacotherapy 1986; 6: 93–103PubMedGoogle Scholar
  5. 5.
    Kokki H, Nikanne E, Ahonen R. The feasibility of pain treatment at home after adenoidectomy with ketoprofen tablets in small children. Paediatr Anaesth 2000; 10: 531–5PubMedCrossRefGoogle Scholar
  6. 6.
    Kokki H, Le Liboux A, Jekunen A, et al. Pharmacokinetics of ketoprofen syrup in small children. J Clin Pharmacol 2000; 40: 354–9PubMedCrossRefGoogle Scholar
  7. 7.
    Kokki H, Tuomilehto H, Tuovinen K. Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes. Br J Anaesth 2000; 85: 836–40PubMedCrossRefGoogle Scholar
  8. 8.
    Ishizaki T, Sasaki T, Suganuma T, et al. Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration. Eur J Clin Pharmacol 1980; 18: 407–14PubMedCrossRefGoogle Scholar
  9. 9.
    Debruyne D, Hurault de Ligny B, Ryckelynck JP, et al. Clinical pharmacokinetics of ketoprofen after single intravenous administration as a bolus or infusion. Clin Pharmacokinet 1987; 12: 214–21PubMedCrossRefGoogle Scholar
  10. 10.
    World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. 52nd World Medical Association, General Assembly; 2000 Oct; Edinburgh, ScotlandGoogle Scholar
  11. 11.
    Upton RA, Buskin JN, Guentert TW, et al. Convenient and sensitive high-performance liquid chromatography assay for ketoprofen, naproxen and other allied drugs in plasma or urine. J Chromatogr 1980; 190: 119–28PubMedCrossRefGoogle Scholar
  12. 12.
    Akaike H. An information criterion (AIC). Math Sci 1976; 14: 5–9Google Scholar
  13. 13.
    Kokki H, Tuomilehto H, Karvinen M. Pharmacokinetics of ketoprofen following oral and intramuscular administration in young children. Eur J Clin Pharmacol 2001; 57: 643–7PubMedCrossRefGoogle Scholar
  14. 14.
    Nahata MC, Durrell DE, Powell DA, et al. Pharmacokinetics of ibuprofen in febrile children. Eur J Clin Pharmacol 1991; 40: 427–8PubMedCrossRefGoogle Scholar
  15. 15.
    Kelley MT, Walson PD, Edge JH, et al. Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clin Pharmacol Ther 1992; 52: 181–9PubMedCrossRefGoogle Scholar
  16. 16.
    Montgomery CJ, McCormack JP, Reichert CC, et al. Plasma concentrations after high-dose (45mg kg-1) rectal acetaminophen in children. Can J Anaesth 1995; 42: 982–6PubMedCrossRefGoogle Scholar
  17. 17.
    van der Marel CD, van Lingen RA, Pluim MA, et al. Analgesic efficacy of rectal versus oral acetaminophen in children after major craniofacial surgery. Clin Pharmacol Ther 2001; 70: 82–90PubMedCrossRefGoogle Scholar
  18. 18.
    Barbanoj MJ, Antonijoan RM, Gich I. Clinical pharmacokinetics of dexketoprofen. Clin Pharmacokinet 2001; 40: 245–62PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2003

Authors and Affiliations

  1. 1.Department of Anaesthesiology and Intensive CareKuopio University HospitalKuopioFinland
  2. 2.Department of PharmaceuticsUniversity of KuopioKuopioFinland

Personalised recommendations