Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia

Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

“…In our cohort of critically ill patients, the PK of doripenem was best described using a two-compartment model with zero-order input and first-order elimination. Such a disposition model is in agreement with other currently available literature in critically ill patients with conserved renal function (7,9,18,33). Typical V (V 1 ϩ V 2 ) of doripenem in our cohort was 0.47 liters/kg (range, 0.14 to 1.7 liters/kg), which is generally consistent with other reports in critically ill patients with conserved renal function (0.30 to 0.54 liters/kg) (7,9,18,33).…”

“…Such a disposition model is in agreement with other currently available literature in critically ill patients with conserved renal function (7,9,18,33). Typical V (V 1 ϩ V 2 ) of doripenem in our cohort was 0.47 liters/kg (range, 0.14 to 1.7 liters/kg), which is generally consistent with other reports in critically ill patients with conserved renal function (0.30 to 0.54 liters/kg) (7,9,18,33). This estimate is considerably larger than that previously described in healthy volunteers (0.22 to 0.24 liters/kg) (34,35) and noncritically ill patients (0.18 to 0.24 liters/kg) (17,(36)(37)(38).…”

“…The typical CL of doripenem in this cohort was 0.14 liters/kg/h (range, 0.06 to 0.45 liters/kg/h), which is generally consistent with that reported in critically ill patients with conserved renal function (0.12 to 0.25 liters/kg/h) (7,9,18,33). However, this estimate is notably lower than that previously described in healthy volunteers (0.22 to 0.25 liters/kg/h) (34,35) and noncritically ill patients (0.16 to 0.25 liters/kg/h) (8,(36)(37)(38).…”

“…However, the appropriateness of this dosing regimen is disputable, as it is based on PK/PD data derived from earlier studies which mostly recruited heterogeneous cohorts of healthy volunteers and noncritically ill Caucasian patients (3)(4)(5)(6). Importantly, results of subsequent PK/PD studies suggest that current recommendations may be grossly flawed in critically ill patients and that optimal dosing requirements may significantly differ from that initially proposed (7)(8)(9).…”

Pharmacodynamics Modeling To Optimize Dosage Regimens of Sulbactam

“…The concentrations of sulbactam were determined by the method of Bawdon and Madsen (6). The method of PK analysis is described in detail elsewhere (7). In brief, differential equations describing a three-compartment infusion model were solved numerically using Taylor series expansion (8), using the Visual Basic programming language in Microsoft Excel, and PK parameters were obtained by minimizing the objective functions of the sum of squared errors (SSE) of logarithmically transformed data using random heuristic optimization (9,10).…”