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

Abstract

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 infinity 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 microgram/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.

Pharmacokinetic profile of controlled release ketoprofen in elderly patients.

“…However plasma concentrations in elderly patients were higher than in young healthy male volunteers (Houghton etal., 1984b) following repeated dosing with controlled release ketoprofen (Figure 2). Mean peak plasma concentrations (5.6 ,ug ml-[ and 6.3 ,ug ml-' on days 1 and 10, respectively) were higher than those reported in young male volunteers given similar treatment, but similar to those reported in young volunteers following repeated administration (50 mg four times daily) of conventionally formulated ketoprofen (Upton et al, 1981;Ishizaki et al, 1980), and markedly lower than following a single oral 100 mg dose of ketoprofen (Ishizaki et al, 1980). Peak plasma ketoprofen concentrations occurred 2 h later in elderly patients (7.8 h) than in young healthy volunteers (5.8 h) following repeated administration of controlled release ketoprofen (Houghton et al, 1984b).…”

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology

“…Ketoprofen (KPR) is a non-steroidal anti-inflammatory drug commonly used in treatment of pain and inflammation. Being a Biopharmaceutics Classification System Class II drug, dissolution is the ratelimiting step for absorption of orally administered KPR and hence was utilized as a model compound (26). Various techniques to increase solubilization have been explored including formulation of solid lipid nanoparticles using waxes and lecithin (27), dispersing in pellets using macrogols (28), hot-melt extrusion coupled with a cyclodextrin (29), self-emulsifying drug delivery systems (30), and lyophilization (31,32).…”

Analgesic-induced Asthma Caused by 2.0% Ketoprofen Adhesive Agents, But Not by 0.3% Agents.

“…The renal contribution to th( plasma clearance of free ketoprofen is thought to be about 109? and ketoprofen is excreted via urine as a form of ketoprofer glucuronide (9). In addition to oral, intramuscular and recta administration, transdermal absorption type ketoprofen adhe sive patches or skin lotion have becomeknownto be ralated tc analgesic-induced asthma.…”