ABSTRACT
A predictive parameter of beta-lactam therapeutic efficacy is the time (T > MIC) while antibiotic serum concentrations are above the MIC of suspected bacteriological agents. This led us to carry out a randomised open study to compare the usually used intermittent administration of Tazocin (three injections of 4 g/0.5 g a day) and continuous perfusion of 12 g/1.5 g a day by calculating these T > MIC. Patients from digestive reanimation department were randomised within two arms: continuous or intermittent administration. Sixteen takings of blood were executed over a forty-hour period. After liquid/liquid extraction, piperacillin and tazobactam serum concentrations were determined by HPLC with a reversed phase column (C18) and a UV spectrophotometry detection. Then, from the time-concentration curves we have evaluated the T > MIC for an enterobacteria (MIC = 8 micrograms/mL) and for Pseudomonas (MIC = 16 micrograms/mL). Concerning intermittent administration T > MIC were 74% (c > MICenterobacteria) and 62% (c > MICPseudomonas). These percentages in the continuous arm were 100% (c > MICenterobacteria) and 99% (c > MICPseudomonas). Tazobactam concentrations were low and even undetectable between each injection in the intermittent administration arm. This was not found within the continuous administration arm. In conclusion, for the intermittent administration, we observed some long periods occurring before each injection while antibiotic concentrations were under the MIC of most bacteria. During these same periods tazobactam concentrations were under the efficacy threshold. These periods were not observed within the continuous administration arm.
Subject(s)
Bacterial Infections/drug therapy , Penicillanic Acid/administration & dosage , Piperacillin/administration & dosage , Adolescent , Adult , Aged , Area Under Curve , Bacteria, Anaerobic , Drug Administration Schedule , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/blood , Drug Therapy, Combination/pharmacokinetics , Drug Therapy, Combination/therapeutic use , Enterobacteriaceae Infections/drug therapy , Female , Gram-Positive Bacterial Infections/drug therapy , Humans , Infusions, Intravenous , Male , Microbial Sensitivity Tests , Middle Aged , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/blood , Penicillanic Acid/pharmacokinetics , Penicillanic Acid/therapeutic use , Piperacillin/blood , Piperacillin/pharmacokinetics , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug CombinationABSTRACT
The aim of this study was to describe an high-performance liquid chromatographic assay for the simultaneous determination of two HIV protease inhibitors, saquinavir and ritonavir, in human serum. The method involved extraction of ritonavir and saquinavir from serum with the aid of solid-phase extraction C18 cartridges followed by high-performance liquid chromatography with a C8 column and ultraviolet detection set at a wavelength of 240 nm. The assay was linear and has been validated over the concentrations range of 0.5-32 microg/ml for ritonavir and 0.075-4.8 microg/ml for saquinavir, from 600 microl serum extracted. In future, the assay will be used to support human population pharmacokinetic studies, and therapeutic drug monitoring for ritonavir and saquinavir.
