Pharmacokinetics and relative bioavailability after single dose administration of 25 mg ketoprofen solution as compared to tablets.
The relative bioavailability of ketoprofen from a liquid formulation as compared to a tablet formulation as reference after single oral dose administration was investigated in 16 healthy male subjects. The subjects received in a randomized, crossover design during one study period of 5 days 2.5 mg of ketoprofen as tablet or liquid formulation administered as single dose with a washout interval of 48 h. The plasma concentrations of S(+)- and R(-)-ketoprofen were determined before and up to 24 h post-administration. S(+)- and R(-)-ketoprofen in the collected plasma samples was determined using an internally standardized validated HPLC method. Regarding the geometric mean concentration-time courses there were no relevant differences between the two ketoprofen enantiomers for both formulations. Remarkable differences in the shape of concentration-time courses between the two formulations were found with higher Cmax (by about 70%) and earlier tmax (by 15 min) values for the ketoprofen solution. The treatments were widely equivalent with regard to AUC. The quotients of geometric means as well as 90% confidence intervals for AUC of R(-)-ketoprofen were 95.72% (92.55-99.00%) and for S(+)-ketoprofen 94.23% (89.91-98.76%). The administration of the ketoprofen solution resulted earlier in higher concentrations (by about 70%) for both enantiomers, whereas the extent of absorption expressed by AUC was nearly the same (about 95%) as compared to the equimolar tablet formulation. The differences between the two formulations for Cmax,norm and tmax were statistically significant.
Stiegler
S
S
Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Grünstadt, Germany.
Birkel
M
M
Jost
V
V
Lange
R
R
Lücker
P W
PW
Wetzelsberger
N
N
D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D012996:Solutions; D013237:Stereoisomerism; D013607:Tablets
D012996:Solutions; D013607:Tablets; D007660:Ketoprofen