NCT01401010

Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients

Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients With Possible Bacterial Infection

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Gary E. Stein, Pharm.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Primary: To determine the serum pharmacokinetics (PK) of doripenem in febrile neutropenic patients. Secondary: Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT)\> minimum inhibitory concentration (MIC))

Detailed description

Background: Doripenem is a group 2 carbapenem with enhanced in vitro activity against Gram-negative bacteria including Pseudomonas aeruginosa. Currently, there is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia. Objectives: To conduct a pharmacokinetic and safety evaluation of two doses of doripenem in febrile neutropenic patients and provide probability estimates of attaining effective drug exposure against common Gram-negative pathogens. Methods: We obtained multiple blood samples from 12 adult patients with febrile neutropenia who were receiving either 500 mg or 1000 mg of doripenem IV over 4-hours every 8 hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6 and 8 hours after initiation of a dose by a validated HPLC assay. The derived pharmacokinetic (PK) parameters from these serum levels were utilized to perform a 5000 patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008 to 64 mg/L to determine probability estimates of time of free drug concentration \> MIC (fT\>MIC). Results: The mean PK parameters in these patients were a volume of distribution (Vd) of 43.9L, an elimination rate constant (k) of 0.37 hr -1, a total clearance (Cl) of 14.4 L/h, and an area under the concentration-time curve (AUC) of 57.6 mg∙h/L. An optimal probability of target attainment (40% fT\>MIC) of 90% was obtained against bacteria with MICs ≤ 2.0 and ≤ 4.0 mg/L with 500 mg and 1000 mg doses, respectively. Adverse events associated with doripenem were not observed in these patients. Conclusions: The findings from this analysis of doripenem suggest that higher doses as well as prolonged infusions may be necessary to optimally treat selected Gram-negative bacteria (eg. Pseudomonas aeruginosa) in patients with febrile neutropenia

Conditions

• Febrile Neutropenia

Interventions

Type	Name	Description
DRUG	Doripenem	500 mg every 8 hours
DRUG	doripenem	1000 mg every 8 hours

Timeline

• Start date: 2010-08-01
• Primary completion: 2012-02-01
• Completion: 2012-02-01
• First posted: 2011-07-25
• Last updated: 2015-10-14
• Results posted: 2012-06-05

Locations

1 site across 1 country: United States