European Journal of Clinical Pharmacology

, Volume 18, Issue 5, pp 407–414 | Cite as

Pharmacokinetics of ketoprofen following single oral, intramuscular and rectal doses and after repeated oral administration

  • T. Ishizaki
  • T. Sasaki
  • T. Suganuma
  • Y. Horai
  • K. Chiba
  • M. Watanabe
  • W. Asuke
  • H. Hoshi
Originals

Summary

The pharmacokinetics of ketoprofen was studied in the same healthy subjects after single oral, intramuscular and rectal doses, and after repeated oral administration. No significant difference in the mean t1/2 (1.13–1.27 h) was observed after the different modes of administration. The mean [AUC]0 after rectal administration of a suppository showed the minimum significant difference (p<0.05) from that after oral administration of the capsule. The apparent volume of distribution (Vd/F) was approximately 10–15% of body weight. The renal contribution (mean, 0.10–0.15 ml/min/kg) to the plasma clearance of free ketoprofen was assumed to be, at most, 8.3–12.9%. The projected cumulative excretion of total (free plus conjugated) ketoprofen via urine exceeded 63–75% of the dose, of which approximately 90% was ketoprofen glucuronide. A mean of 71–96% and 73–93% of the oral capsule was estimated to be systemically available after administration of the intramuscular preparation and rectal suppository, respectively. In four of seven subjects, CPK concentration was elevated after the intramuscular injection. The mean steady-state concentration of ketoprofen in plasma ranged from 0.43 to 5.62 µg/ml after the final dose of a 50 mg q.i.d. regimen. The disposition data and plasma levels observed at steady-state were in agreement with those predicted from the single oral dose study. The accumulation ratio was 1.08±0.08. The results suggest that the rectal suppository can be recommended as an extravascular mode of administration of this drug.

Key words

ketoprofen pharmacokinetics relative bioavailability single doses repeated doses prediction of kinetics 

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Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • T. Ishizaki
    • 1
  • T. Sasaki
    • 1
  • T. Suganuma
    • 1
  • Y. Horai
    • 1
  • K. Chiba
    • 1
  • M. Watanabe
    • 1
  • W. Asuke
    • 2
  • H. Hoshi
    • 3
  1. 1.Division of Clinical Pharmacology, Clinical Research InstituteNational Medical Center HospitalTokyoJapan
  2. 2.Department of Biochemical Pharmacology, Faculty of Pharmaceutical ScienceUniversity of ChibaChibaJapan
  3. 3.Department of Pharmaceutical ChemistryKyoto College of PharmacyKyotoJapan

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