AIM: The aim of this study was to develop a vancomycin population pharmacokinetic model in adult obese patients and propose covariate-based dosing individualization in order to maximize the achievement of the newly recommended PK/PD target, according to a revised consensus guideline from 2020. METHODS: Therapeutic drug monitoring data from initial vancomycin therapy (first 3 days of treatment) in adult obese (BMI ≥ 30 kg/m2) patients from 2013 to 2022 were analyzed using a non-linear mixed-effects modeling method, and Monte Carlo simulations were then used to find the optimal dosage maximizing the PK/PD target attainment. RESULTS: A total of 147 vancomycin serum levels obtained from 138 patients were included in the analysis. Based on the covariate model diagnosis among all tested variables, no reliable predictor of vancomycin volume of distribution (Vd) was identified, while clearance (CL) was positively correlated with eGFR and lean body mass. Creatinine-based eGFR predicted vancomycin CL better than cystatin C-based eGFR. The median (interquartile range) value from conditional modes of individual estimates of Vd, CL, and elimination half-life in our population was 74.0 (70.5-75.4) L, 6.65 (4.95-8.42) L/h, and 7.7 (6.0-10.0) h, respectively. CONCLUSION: We proposed dosing individualization based on the covariate found in order to maximize the achievement of the newly recommended PK/PD target of the AUC/MIC ratio of 400-600. Clinical pharmacy/pharmacology interventions may lead to an improvement in vancomycin dosing with a reflection in PK/PD target attainment.

• Keywords
• Monte Carlo simulation, clinical pharmacy, glomerular filtration rate, lean body mass, non-linear mixed-effects modeling, obesity, therapeutic drug monitoring,
• Publication type
• Journal Article MeSH

OBJECTIVES: Due to the high interindividual variability in vancomycin pharmacokinetics, optimisation of its dosing is still challenging. This study aimed to explore vancomycin pharmacokinetics in adult patients and to propose an easy applicable dosing nomogram for initial treatment. METHODS: Vancomycin pharmacokinetics was calculated in a two-compartmental model based on therapeutic drug monitoring data. A linear regression model was used to explore the relationship between vancomycin elimination half-life and glomerular filtration rate estimated according the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: In the whole study population (n=66), vancomycin volume of distribution, clearance and half-life median (IQR) values were 0.69 (0.58-0.87) L/kg, 0.031 (0.022-0.050) L/h/kg and 14.4 (9.5-25.2) hours, respectively. Vancomycin half-life was associated with glomerular filtration rate (r2=0.4126, p<0.0001) according to the formula: t1/2 (h) = -0.247×eGFRCKD-EPI (mL/min/1.73 m2)+32.89. This relationship was used to construct a dosing nomogram. CONCLUSIONS: We propose an easy-to-use dosing nomogram for vancomycin therapy initiation that allows individualisation of the dosing interval with respect to the administered dose size and functional renal status.

• Keywords
• CKD-EPI, dosing nomogram, glomerular filtration, pharmacokinetics, therapeutic drug monitoring, vancomycin,
• MeSH
• Anti-Bacterial Agents * MeSH
• Adult MeSH
• Glomerular Filtration Rate MeSH
• Kidney physiology   MeSH
• Humans MeSH
• Drug Monitoring MeSH
• Vancomycin * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Vancomycin * MeSH