Effect of cyclohexanone derivatives on percutaneous absorption of ketoprofen and indomethacin.
The promoting effect of cyclohexanone derivatives on the percutaneous absorption of ketoprofen and indomethacin from gel ointments was investigated in rats. Drug absorption was markedly enhanced by the addition of 2-tert-butylcyclohexanone. Promoting activities of 2,6-dimethyl and 4-tert-butylcyclohexanone were also observed, but their effects were significantly lower than that of the 2-tert-butyl derivative. The effect of side chain length at the 2-position of the cyclohexanone ring on the percutaneous absorption of these drugs was determined similarly using a series of 2-n-alkylcyclohexanones. Pronounced effects were observed in the case of 2-n-octylcyclohexanone, suggesting that a chain length of eight carbons is an important factor for absorption enhancement in this series. The extent of absorption enhancement was found to be an almost linear function of 2-n-octycyclohexanone concentrations in the range from 0 to 10%.
Akitoshi
Y
Y
Faculty of Pharmaceutical Science, Hoshi University, Tokyo, Japan.
Takayama
K
K
Machida
Y
Y
Nagai
T
T
D000279:Administration, Cutaneous; D000818:Animals; D003512:Cyclohexanones / Q000008:administration & dosage / Q000493:pharmacokinetics; D015195:Drug Design; D007213:Indomethacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D010666:Phenylpropionates / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D013329:Structure-Activity Relationship
D003512:Cyclohexanones; D010666:Phenylpropionates; D007660:Ketoprofen; D007213:Indomethacin