Infect Chemother.  2014 Mar;46(1):21-29. 10.3947/ic.2014.46.1.21.

Underestimation of the Calculated Area Under the Concentration-Time Curve Based on Serum Creatinine for Vancomycin Dosing

• Jin SJ
• Yoon JH
• Ahn BS
• Chung JA
• Song YG

• KMID: 2170456
• DOI: http://doi.org/10.3947/ic.2014.46.1.21

Abstract

BACKGROUND
The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC24) to the MIC (AUC24/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC24 (cAUC24) using the creatinine clearance (CLcr) differs from the ssAUC24 based on the individual pharmacokinetic data estimated by a commercial software.
MATERIALS AND METHODS
The cAUC24 was compared with the ssAUC24 with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC24 and ssAUC24 and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC24/MIC of 400 or higher was compared between the cAUC24 and ssAUC24 for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher.
RESULTS
The cAUC24 was significantly lower than the ssAUC24 (392.38 vs. 418.32 mg.hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC24/MIC and 100% for the ssAUC24/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC24/MIC and 71.8% for the ssAUC24/MIC at a daily vancomycin dose of 4,000 mg.
CONCLUSIONS
The cAUC24 using the calculated CLcr is usually underestimated compared with the ssAUC24 based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC24, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.

Keyword

Vancomycin; Pharmacodynamics; Area under curve; Drug monitoring, Therapeutic

MeSH Terms

Area Under Curve
Body Mass Index
Creatinine*
Drug Monitoring
Humans
Vancomycin*
Creatinine
Vancomycin

Figure

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  Figure 1 Relationship between the steady-state 24-hour AUC (ssAUC24) and steady-state trough concentration of vancomycin (A), and between the calculated AUC (cAUC24) and steady-state trough concentration of vancomycin (B).

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  Figure 2 Probability (%) of reaching target ssAUC24/MIC (A) and cAUC24/MIC (B) values of 400 or higher for different MICs (0.5, 1.0, and 2.0 mg/L) and daily vancomycin doses (2,000, 2,500, 3,000, 3,500, and 4,000 mg) by simulation in patients with a trough concentration of 15 to 20 mg/L.

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  Figure 3 Percent distribution of the vancomycin MIC (by microbroth dilution method using Vitek 2 system [bioMerieux, Marcy 1'Etoile, France]) against MRSA isolated from July 2007 to June 2010 at the Gangnam Severance Hospital.

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