Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients

• Published in: Journal of chemotherapy (Florence) Vol. 23; no. 5; pp. 277 - 281
• Main Authors: Verdier, M C, Tribut, O, Tattevin, P, Michelet, C, Bentué-Ferrer, D
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Ltd 01.10.2011; Maney Publishing
• Subjects: Adult; Aged; Aged, 80 and over; Amoxicillin; Amoxicillin - administration & dosage; Amoxicillin - blood; Amoxicillin - pharmacokinetics; Anti-Bacterial Agents; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - blood; Anti-Bacterial Agents - pharmacokinetics; Bacterial Infections; Bacterial Infections - complications; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Bacterial Infections - physiopathology; Cloxacillin; Cloxacillin - administration & dosage; Cloxacillin - blood; Cloxacillin - pharmacokinetics; Creatinine; Creatinine - blood; Creatinine - metabolism; Drug Administration Schedule; Endocarditis, Bacterial; Endocarditis, Bacterial - complications; Endocarditis, Bacterial - drug therapy; Endocarditis, Bacterial - microbiology; Endocarditis, Bacterial - physiopathology; Female; Human health and pathology; Humans; Infectious diseases; Infusions, Intravenous; Intensive Care Units; Life Sciences; Male; Medical Records; Methicillin-Resistant Staphylococcus aureus; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Middle Aged; Renal Insufficiency; Renal Insufficiency - complications; Reproducibility of Results; Retrospective Studies; Severity of Illness Index; Streptococcal Infections; Streptococcal Infections - complications; Streptococcal Infections - drug therapy; Streptococcal Infections - microbiology; Streptococcal Infections - physiopathology; intravenous administration; pharmacokinetic variability; Cloxacillin; Therapeutic Drug Monitoring; Amoxicillin
• ISSN: 1120-009X; 1973-9478
• DOI: 10.1179/joc.2011.23.5.277

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.