ORIGINAL RESEARCH

Parameters of vancomycin pharmacokinetics in postoperative patients with renal dysfunction: comparing the results of a pharmacokinetic study and mathematical modeling

Ramenskaya GV1, Shokhin IE1,3, Lukina MV2, Andrushishina TB2, Chukina MA2, Tsarev IL2, Vartanova OA2, Morozova TE2
About authors

1 Department of Pharmaceutical and Toxicological Chemistry, Institute of Pharmacy,
Sechenov First Moscow State Medical University (Sechenov University), Moscow

2 Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Faculty of General Medicine,
Sechenov First Moscow State Medical University (Sechenov University), Moscow

3 Center of Pharmaceutical Analytics Ltd., Moscow

Correspondence should be addressed: Maria V. Lukina
Bolshaya Pirogovskaya, 2 bl.4, Moscow, 119435; ur.xednay@0102kul-iram

About paper

Acknowledgements: the authors wish to thank Oleg V. Babenko, Chief Physician of the University Clinical Hospital No.1 of Sechenov First Moscow State Medical University for providing an opportunity to carry out our research

Received: 2018-05-16 Accepted: 2018-08-25 Published online: 2018-10-11
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Mathematical modeling of pharmacokinetic (PK) and pharmacodynamic (PD) parameters essential for establishing correct dosing regimens is an alternative to pharmacokinetic studies (PKS) adopted in the clinical setting. The aim of this work was to compare the values of PK parameters for vancomycin obtained in an actual PKS and through MM in postoperative patients with kidney injury. Our prospective study included 61 patients (47 males and 14 females aged 60.59 ± 12.23 years). During PKS, drug concentrations at steady state Сtrough and Cpeak were measured by high-performance liquid chromatography followed by the calculation of the area under the plasma concentration-time curve AUC24. For mathematical modeling, a single-compartment model was employed; PK parameters were estimated using R 3.4.0. The values of Ctrough measured 48 h after the onset of antibiotic therapy during PKS were significantly lower than those predicted by MM (р = 0.004). In a group of patients with acute kidney injury (AKI), AUC24 measured at the end of treatment was significantly higher than its value predicted by MM (р = 0.011). The probability of achieving the target AUC24 to MIC ratio of over 400 μg•h /ml is higher in the group of patients with Ctrough = 10–15 μg /ml. Our findings confirm that the use of MM in postoperative patients with renal dysfunction is limited and therapeutic drug monitoring should be used instead.

Keywords: pharmacokinetic study, vancomycin pharmacokinetics, mathematical modeling, acute kidney injury, surgical patients

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