Differences in antimicrobial drug exposure in patients with various degrees of renal function based on recommendations from dosing references.
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.


METHODS
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)).


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).


CONCLUSIONS
Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate-to-severe renal impairment.
Bonapace
Charles R
CR
Anti-Infective Research Laboratory, College of Pharmacy, Medical University of South Carolina, Charleston 29425, USA.
White
Roger L
RL
Frich
Lawrence V
LV
Bosso
John A
JA
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D003198:Computer Simulation; D003404:Creatinine / Q000097:blood; D024841:Fluoroquinolones; D017408:Guidelines as Topic; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism*; D007677:Kidney Function Tests; D007769:Lactams; D008954:Models, Biological; D011485:Protein Binding; D012015:Reference Standards
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001798:Blood Proteins; D024841:Fluoroquinolones; D007769:Lactams; D003404:Creatinine