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Population pharmacokinetics of daptomycin
Barry Dvorchik1, Robert D Arbeit, Julia Chung
1Cubist Pharmaceuticals, Inc., Lexington, Massachusetts 02421, USA. bdvorchi@tampabay.rr.com
Antimicrobial Agents and Chemotherapy
|July 27, 2004
Summary
Renal function, body temperature, and sex significantly impact daptomycin pharmacokinetics (PK). Dosing adjustments are recommended for patients with severe kidney impairment or undergoing dialysis.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Drug Metabolism
Background:
- Daptomycin is a key antibiotic for treating Gram-positive infections.
- Understanding interindividual variability in daptomycin pharmacokinetics (PK) is crucial for optimizing therapy.
- Factors influencing daptomycin PK require further elucidation.
Purpose of the Study:
- To identify key covariates affecting daptomycin pharmacokinetics (PK) in patients.
- To develop a population PK model for daptomycin.
- To inform daptomycin dosing strategies based on patient characteristics.
Main Methods:
- Combined data from nine Phase 1 and six Phase 2/3 clinical trials.
- Utilized a two-compartment model with first-order elimination for PK analysis.
- Assessed over 30 potential covariates, including renal function, body temperature, and sex.
Main Results:
- Daptomycin plasma clearance (CL) is influenced by renal function, body temperature, and sex.
- Renal function, particularly creatinine clearance, is the most significant factor affecting daptomycin CL.
- Daptomycin CL is substantially reduced in patients undergoing dialysis and is related to body weight and acute infection status.
Conclusions:
- Daptomycin dosing should be weight-based (mg/kg).
- Modified dosing regimens are necessary for patients with severe renal impairment and those on dialysis.
- While sex impacts CL, it is not clinically significant for daptomycin outcomes.