Comparison of the pharmacokinetics and pharmacodynamic profile of carumonam in cystic fibrosis patients and healthy volunteers.

Jürgen B Bulitta, Stephen B Duffull, Cornelia B Landersdorfer, Martina Kinzig, Ulrike Holzgrabe, Ulrich Stephan, George L Drusano, Fritz Sörgel

IBMP-Institute for Biomedical and Pharmaceutical Research, D-90562 Nürnberg-Heroldsberg, Germany.

Diagnostic microbiology and infectious disease 2009 Oct

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Our objectives were to compare the pharmacokinetics (PK) of carumonam, a monobactam, between cystic fibrosis (CF) patients and healthy volunteers and assess its pharmacodynamic profile. We studied 10 adult CF patients and 18 healthy volunteers of similar body size (dose: 2.166 g of carumonam as 15-min intravenous infusion). High performance liquid chromatography with ultraviolet detection (HPLC-UV) was used for drug analysis and NONMEM (ICON, Ellicot City, MD) for population PK and Monte Carlo simulation with targets between > or =20% and 100% free time above MIC (fT > MIC). Unscaled renal clearance was 24% higher in CF patients. Lean body mass and creatinine clearance explained the difference in average clearance and volume of distribution between both subject groups. For a daily dose of 6 g per 70 kg of total body weight, 15-min infusions q8h achieved robust (>90%) probabilities of target attainment (PTAs) (target, 60% fT > MIC) for MICs < or =3 mg/L in CF patients and < or =6 mg/L in healthy volunteers. At the same dose, 4-h infusions q8h achieved robust PTAs up to markedly higher MICs < or =8 to 12 mg/L in CF patients and < or =16 mg/L in healthy volunteers.

Citation

Jürgen B Bulitta, Stephen B Duffull, Cornelia B Landersdorfer, Martina Kinzig, Ulrike Holzgrabe, Ulrich Stephan, George L Drusano, Fritz Sörgel. Comparison of the pharmacokinetics and pharmacodynamic profile of carumonam in cystic fibrosis patients and healthy volunteers. Diagnostic microbiology and infectious disease. 2009 Oct;65(2):130-41