Mathematical modeling of vancomomycin pharmacokinetics parameters: opportunities and comparison with the results of therapeutic drug monitoring

The purpose of a prospective observational study is to compare the pharmacokinetic parameters of vancomycin, obtained by therapeutic drug monitoring and mathematical modeling of surgical patients with renal dysfunction. A total of 61 patients (men - 47 people, women - 14) aged 60.59 ± 12.23 years were examined. The study participants were divided into two groups: the first with acute renal damage (66.6%), the second without it (33.4%). Equilibrium residual and peak concentrations of vancomycin were determined by high performance liquid chromatography. It was established that the values of the equilibrium residual concentrations of vancomycin after 48 hours from the start of therapy were significantly lower than the values obtained by mathematical modeling in the group of patients with acute renal damage (p=0.004). The values of the equilibrium residual concentrations at the time of completion of vancomycin therapy in groups with acute renal damage (p=0.092) and without it (p=0.087) do not differ significantly. The actual values of the area under the pharmacokinetic curve for 24 hours were significantly higher than the calculated level in the groups with acute renal damage (p=0.011) and close to reliable in the group without it (p=0.056). When equilibrium residual concentrations of 10-15 µg/ml are reached, the ratio of the area under the pharmacokinetic curve for 24 hours to the minimum inhibitory concentration reaches target values (more than 400 µg*h/ml) after 48 hours from the start of therapy and at the time of completion of antibiotic therapy. Differences in the actual values of pharmacokinetic parameters and those obtained by the method of mathematical modeling indicate the need for mandatory use of therapeutic drug monitoring in patients with renal dysfunction.

vancomycin pharmacokinetics, mathematical modeling, therapeutic drug monitoring, renal dysfunction

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29. Matzke G.R., McGory R.W., Halstenson C.E., Keane W.F. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984; 25(4): 433-437.

30. Moise-Broder P.A., Forrest A., Birmingham M.C., et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin. Pharmacokinet., 2004; 43: 925-942.

31. Murphy J.E., Gillespie D.E., Bateman C.V. Predictability of vancomycin trough concentrations using seven approaches for estimating pharmacokinetic parameters. Am. J. Health Syst. Pharm., 2006; 63: 2365-70.

32. Neely M.N., Youn G., Jones B., Jelliffe R.W., Drusano G.L., Rodvold K.A., et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother., 2014; 58(1): 309-316.

33. Pai M.P., Neely M., Rodvold K.A., Lodise T.P. Innovative approaches to optimizing the delivery of vancomycin in individual patients. Advanced drug delivery reviews, 2014; 77: 50-57.

34. Patel N., Pai M.P., Rodvold K.A., Lomaestro В., Drusano G.L., Lodise T.P. Vancomycin: we can't get there from here. Clinical infectious diseases, 2011; 52(8): 969-974.

35. Prybylski J.P. Vancomycin trough concentration as a predictor of clinical outcomes in patients with Staphylococcus aureus bacteremia: a meta-analysis of observational studies. Pharmacotherapy: J. of Human Pharmacology and Drug Therapy, 2015; 35(10): 889-898.

36. Rybak M., et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am. J. of Health-System Pharmacy, 2009; 66(1): 82-98.