Effect of sodium diclofenac on the bioavailability of amoxicillin.
The aim of this study was to evaluate the effect of sodium diclofenac on the bioavailability of amoxicillin. In this randomised, crossover study with a 1-week washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil) (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac (Voltaren) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, 12 and 24h following drug administration. High-performance liquid chromatography with ultraviolet detection was used to quantify plasma amoxicillin concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic parameters area under the plasma concentration-time curve (AUC), maximum plasma concentration observed during the 24-h study period (C(max)) and renal clearance (CL) were analysed by analysis of variance, and time at which C(max) occurred (T(max)) and volume of distribution (VD) were analysed by Wilcoxon test (P<0.05). For Group 1, the mean (+/- standard deviation) AUC(0-24), C(max) and T(max) values were 3391.8+/-1186.7 microg min/mL, 17.3+/-6.5 microg /mL and 121.5+/-20.6 min, respectively; and for Group 2, the values were 2918.4+/-1024.8 microg min/mL, 15.5+/-5.8 microg /mL and 136.5+/-30.0 min, respectively. Lower values of AUC and C(max) were observed for Group 2 (P<0.05). CL of amoxicillin increased (P< 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere with amoxicillin renal excretion. In conclusion, sodium diclofenac can significantly reduce the bioavailability of amoxicillin.
de Cássia Bergamaschi
Cristiane
C
Piracicaba Dental School, University of Campinas, Department of Pharmacology, Anesthesiology and Therapeutics, Av. Limeira 901, 13414-903 Piracicaba, SP, Brazil.
Motta
Rogério Heládio Lopes
RH
Franco
Gilson Cesar Nobre
GC
Cogo
Karina
K
Montan
Michele Franz
MF
Ambrosano
Glaúcia Maria Bovi
GM
Rosalen
Pedro Luiz
PL
Del Fiol
Fernando de Sá
Fde S
Groppo
Francisco Carlos
FC
D000328:Adult; D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004008:Diclofenac / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D008297:Male
D004008:Diclofenac; D000658:Amoxicillin