Bioavailability study of fosfosal and codeine administered alone or in combination.
Fosfosal (2-phosphonoxybenzoic acid) is a new salicylic acid derivative which is used for treating inflammatory disease as well as in analgesic therapy. On the other hand, codeine together with acetylsalicylic acid is widely used in patients who require analgesic treatment for mild to moderate pain. The present study was carried out in ten healthy subjects to assess the pharmacokinetic profiles of single oral doses of fosfosal (1,200 mg) and codeine (30 mg) when administered alone or in combination. Blood samples were drawn on each study day and salicylic acid and codeine plasma concentrations were determined by HPLC and enzyme immunoassay methods, respectively. Individual pharmacokinetic parameters were calculated according to standard procedures and the magnitude and rate of bioavailability were tested using a 95% confidence internal approach. Results indicated no statistical differences in any of the kinetic parameters studied except for tmax values which were higher for fosfosal combined with codeine (2 +/- 0.39 h) when compared to fosfosal alone (1.55 +/- 0.35 h). Regarding codeine compared in combination with fosfosal, no significant differences were observed in Cmax and AUC values, while tmax showed a higher value for the combination (1.75 +/- 0.6 vs 0.85 +/- 0.32 h). Although statistical differences in the elimination constant rate and MRT were found between both codeine administrations, these cannot be considered significant in clinical terms. The changes in bioavailability rate observed for both drugs when administered together provide support for the use of this combination in a single formulation.
Ramis
J
J
Research Center, J. Uriach & Cia, S.A., Barcelona, Spain.
Gich
I
I
Torrent
J
J
Mis
R
R
Jané
F
F
Forn
J
J
D000328:Adult; D001682:Biological Availability; D003061:Codeine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010755:Organophosphates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*
D010755:Organophosphates; D009943:Organophosphorus Compounds; C000380:fosfosal; D003061:Codeine