title: Comparative pharmacokinetic and pharmacodynamic profile of piperacillin/tazobactam 3.375G Q4H and 4.5G Q6H.
abstract: When piperacillin/tazobactam has been used to treat hospitalized patients with serious infections, including nosocomial pneumonia caused by Pseudomonas aeruginosa, it has usually been dosed at 3.375 g q4h to provide serum concentrations above commonly encountered organisms' MICs (T > MIC) for at least 40-50% of the dosing interval. Pharmacodynamic principles suggest that a similar efficacy can be realized with extended dosing intervals when a larger dose (e.g. 4.5 g q6h) is administered, which was the objective of this study. Twelve healthy volunteers, 29.4 +/- 8.9 years of age, were enrolled in this multiple-dose, open-labeled, randomized, two-period crossover study. Blood samples were collected after the third dose and concentrations of piperacillin/tazobactam were determined with a validated HPLC method. Pharmacokinetic profiles were determined by noncompartment analysis. T > MIC of piperacillin was calculated for a range of MIC values. Piperacillin/tazobactam was well tolerated in 11 subjects who completed both regimens. The C(max), T(1/2), K, and AUC of P were significantly different according to a paired t test (p < 0.05) between two study regimens. Significant differences (p < 0.05) in tazobactam regimens were noted for C(max), and AUC. The piperacillin/tazobactam regimen of 4.5 g q6h achieved a 44% T > MIC for MIC values of < or = 16 microg/ml, while the 3.375-gram q4h regimen achieved 42% T > MIC, for MIC values of < or = 32 microg/ml. Dosage regimens for treating serious infections can be extended safely and effectively to 4.5 g q6h and obtain at least 40-50% T > MIC in the coverage of pathogens implicated with serious infections, including P. aeruginosa.
authors: Department of Pharmacy Research, Hartford Hospital, Hartford, Conn., USA.
authors: Holly M
authors: HM
authors: Mattoes
authors: Blair
authors: B
authors: Capitano
authors: Myo-Kyoung
authors: MK
authors: Kim
authors: Dawei
authors: D
authors: Xuan
authors: Richard
authors: R
authors: Quintiliani
authors: Charles H
authors: CH
authors: Nightingale
authors: David P
authors: DP
authors: Nicolau
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010878:Piperacillin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000077725:Piperacillin, Tazobactam Drug Combination; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity
chemical_list: D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin