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Differences in antimicrobial drug exposure in patients with various degrees of renal function based on
Charles R Bonapace1, Roger L White, Lawrence V Frich
1Anti-Infective Research Laboratory, College of Pharmacy, Medical University of South Carolina, Charleston 29425, USA.
Study Objective:
To calculate and compare 24-hour area under the unbound drug concentration-time curves (AUC(0-24)) of antimicrobials with dosing recommendations from six commonly used dosing references.
Intervention:
Unbound plasma concentration-time profiles of 13 antimicrobial agents (4 penicillins, 3 cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at steady state using a one-compartment open model for a 70-kg adult based on pharmacokinetic parameters obtained from peer-reviewed literature. Simulations were performed at five levels of creatinine clearance (Cl(cr)).
Measurements And Main Results:
Differences in AUC(0-24) for each antimicrobial agent were noted among the six references at each level of Cl(cr) as well as within references across the range of Cl(cr). In addition, up to 16-fold and 3-fold ranges in AUC(0-24) values were observed for beta-lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Cl(cr) (due to more than one dose and/or dosing interval).
Conclusion:
Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate-to-severe renal impairment.