asancpt / shiny-vtdm Goto Github PK

• Vancomycin TDM KR https://asan.shinyapps.io/vtdm
• Vancomycin TDM KR is open to everyone. We are happy to take your input. Please fork the repo, modify the codes and submit a pull request. https://github.com/shanmdphd/vtdm

This work is largely dependent on the paper published in J Clin Pharm Ther. in 2014.

• Lim HS, Chong YP, Noh YH, Jung JA, Kim YS. Exploration of optimal dosing regimens of vancomycin in patients infected with methicillin-resistant Staphylococcus aureus by modeling and simulation. J Clin Pharm Ther. 2014;39(2):196-203. https://www.ncbi.nlm.nih.gov/pubmed/24428720
• Rybak et al. Therapeutic monitoring of vancomycin in adult patients. American Journal of Health-System Pharmacy. 2009;66(1):82-98. http://www.ajhp.org/content/66/1/82
• "Clinical pharmacokinetics and pharmacodynamics: concepts and applications, 4th edition" Lippincott Williams & Wilkins. 2011. ISBN 978-0-7817-5009-7

The pharmacokinetic parameters from the paper were derived and used in the app as follows:

$$ \begin{split} Creatinine\ CL & = \frac{(140-age) \cdot W (\cdot 0.85\ if\ female)}{72 \cdot Cr} \newline \newline \begin{bmatrix} \eta_1 \newline \eta_2 \newline \eta_3 \end{bmatrix} & \sim MVN \bigg( \begin{bmatrix} 0 \newline 0 \newline 0 \end{bmatrix} , \begin{bmatrix} 0.120 & 0 & 0 \newline 0 & 0.149 & 0 \newline 0 & 0 & 0.416 \end{bmatrix} \bigg) \newline \newline V_1\ (L) & = 33.1 \cdot e^{\eta1} \newline V_2\ (L) & = 48.3 \newline CL\ (L/hr) & = 3.96 \cdot \frac{CCR}{100} \cdot e^{\eta2} \newline Q\ (L/hr) & = 6.99 \cdot e^{\eta3} \newline \newline k_{10}\ (/hr) & = \frac{CL}{V_1} \newline k_{12}\ (/hr) & = \frac{Q}{V_1} \newline k_{21}\ (/hr) & = \frac{Q}{V_2} \newline \newline \lambda_1 & = \frac{k_{10} + k_{12} + k_{21} + \sqrt{(k_{10} + k_{12} + k_{21})^2 - 4 \cdot k_{10} \cdot k_{21}}}{2} \newline \lambda_2 & = k_{10} + k_{12} + k_{21} - \lambda_1 \newline & = k_{10} + k_{12} + k_{21} - \frac{k_{10} + k_{12} + k_{21} + \sqrt{(k_{10} + k_{12} + k_{21})^2 - 4 \cdot k_{10} \cdot k_{21}}}{2} \newline C_1\ (mg/L) & = \frac{\lambda_1 - k_{21}}{V_1 \cdot (\lambda_1 - \lambda_2)} \newline C_2\ (mg/L) & = \frac{k_{21} - \lambda_2}{V_1 \cdot (\lambda_1 - \lambda_2)} \newline During\ infusion &\newline C_p\ (mg/L) &= \frac{Rate}{\lambda_1} \cdot C_1 \cdot (1 - e^{-\lambda_1 \cdot t}) + \frac{Rate}{\lambda_2} \cdot C_2 \cdot (1 - e^{-\lambda_2 \cdot t}) \newline After\ infusion &\newline C_p\ (mg/L) &= \frac{Rate}{\lambda_1} \cdot C_1 \cdot (1 - e^{-\lambda_1 \cdot DUR}) \cdot e^{-\lambda_1 \cdot t} + \frac{Rate}{\lambda_2} \cdot C_2 \cdot (1 - e^{-\lambda_2 \cdot (t-DUR)}) \cdot e^{-\lambda_2 \cdot (t-DUR)} \newline \end{split} $$

(Abbreviation: $AI$, accumulation index; $AUC$, area under the plasma drug concentration-time curve; $CL$, total clearance of drug from plasma; $C_{av,ss}$, average drug concentration in plasma during a dosing interval at steady state on administering a fixed dose at equal dosing intervals; $C_{max}$, highest drug concentration observed in plasma; $Creatinine\ CL$, Cockcroft-Gault creatinine clearance(ml/min/1.73 m^2 ); $MVN$, multivariate normal distribution; $Q$, Intercompartmental clearance; $V$, Volume of distribution (apparent) based on drug concentration in plasma; $W$, body weight (kg); $\eta$, interindividual random variability parameter; $k$, elimination rate constant; $k_a$, absorption rate constant; $\tau$, dosing interval)

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