title: Comparison of the pharmacokinetics and pharmacodynamic profile of carumonam in cystic fibrosis patients and healthy volunteers.
abstract: 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.
authors.affiliation: IBMP-Institute for Biomedical and Pharmaceutical Research, D-90562 Nürnberg-Heroldsberg, Germany.
authors.forename: Jürgen B
authors.initials: JB
authors.lastname: Bulitta
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.forename: Cornelia B
authors.initials: CB
authors.lastname: Landersdorfer
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephan
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001398:Aztreonam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method; D010949:Plasma / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; C044145:carumonam; D001398:Aztreonam