PHARMACOKINETIC PARAMETERS AND KILLING RATES IN SERUM OF VOLUNTEERS RECEIVING AMOXICILLIN, CEFADROXIL OR CEFIXIME ALONE OR ASSOCIATED WITH NIFLUMIC ACID OR PARACETAMOL

Pharmacokinetic parameters and killing rates in serum of volunteers re ceiving amoxicillin, cefadroxil or cefixime alone or associated with n iflumic acid or paracetamol were studied. Niflumic acid (250 mg) or an algesic and antipyretic drugs such as paracetamol (500 mg) are often c ombined with antibiotics to avoid inflammation and pain in acute ear, nose and throat diseases. Pharmacokinetic interactions between these t wo classes of drugs have been described in experimental models, and ex ceptionally in humans. The aim of the present investigation was to stu dy the interactions of these two drugs with three antibiotics (amoxici llin 500 mg x 2, cefadroxil 500 mg x 2, cefixime 200 mg and one placeb o capsule) on pharmacodynamic parameters and on rate of killing in the serum of six healthy volunteers receiving the antibiotic associated o r not with the product in a randomized cross-over double-blind trial. The bacteria most often involved in sinusitis, bronchitis and otitis m edia (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) three target diseases for oral cephalosporins and amoxicillin , were chosen for bacteriological study. Blood samples were obtained a t 0.25, 0.50, 1, 1.5, 2, 4, 6 and 12 h after oral administration of an tibiotics alone or associated with the drugs. There was a wash-out per iod of at least 1 week between the eleven sequences. Antibiotics were measured by two methods: bioassay and high performance liquid chromato graphy (HPLC). All serum samples obtained at peak level, 4 and 6 h wer e tested for killing rate. Area under the time kill curve was calculat ed by the trapezoidal rule method and relative bioactivity in percent was defined as follows: (AUC control - AUC test)/AUC control x 100. No pharmacokinetic interaction was found in the AUC and T-1/2 of the pla sma concentrations of the antibiotics or associated with the drugs, re gardless of dose, as determined by HPLC or microbiological assay. For these beta-lactam antibiotics killing rate was found to be time-depend ent. Bactericidal activity was improved on H. influenzae when cefixime was associated with niflumic acid and became concentration-dependent. A significant concentration relation was also found with niflumic aci d or paracetamol associated with cefixime on Strep. pneumoniae.