Differences in Antimicrobial Drug Exposure in Patients with Various Degrees of Renal Function Based on Recommendations from Dosing References

Study Objective. To calculate and compare 24–hour area under the unbound drug concentration‐time curves (AUC0.24) 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 (Clcr). Measurements and Main Results. Differences in AUC0–24 for each antimicrobial agent were noted among the six references at each level of Clcr as well as within references across the range of Clcr. In addition, up to 16–fold and 3–fold ranges in AUC0–24 values were observed for β‐lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Clcr (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. (Pharmacotherapy 2002;22(9):1097–1104)