Title (srp)

Farmakokinetička ispitivanja mikofenolne kiseline kod pacijenata sa presađenim bubregom


Kundalić, Ana A., 1988


Veličković-Radovanović, Radmila, 1961-
Catić-Đorđević, Aleksandra, 1971-
Cvetković, Tatjana, 1965-
Mitić, Branka, 1962-
Pavlović, Radiša, 1976-

Description (srp)

Mycophenolic acid (MPA) is frequently prescribed as a part ofimmuno suppressive protocols following kid ney transplantation.Significant variability in MPA pharmacokinetics and the differentindividual response emphasize the need for individualized dosingregimens. The goals of this research were the development andvalidat ion of HPLC method for the quantita tiv e analysis of MPA, theidentification of factors that contribute to the interindividualvariability of MPA, the assessment of the frequency and intensity ofadverse effects, the examine association of the salivary conc entration(C SAL ) with the manifeste d a dverse effects, as well as the associationof the plasma and salivary concentration in relation to serum albuminlevels in kidney transplant patients.This research included 102 adult kidney transplant patients. Plasmaand salivary MPA concentrations w ere determined by a validatedHPLC method and LC MS. The NONMEM® software was used forthe population analysis. The obtained model was further investigatedusing Monte Carlo (MC) modeling. Adverse effects of the appliedt herapy were collected through a val ida ted questionnaire. Acorrelation between plasma and salivary MPA concentrations wasestablished using the least squares method.Population pharmacokinetic analysis identified patient age, MPA dailydose, and nifedipine co therapy as significant factors in the variabilityof MPA clearance. Using external validation method, the validity ofthe obtained population model was confirmed. Furthermore, themodel was compared with similar models available in the literatureusing the MC method, which confirmed its va lidity. A higherfrequency of adverse effects was recorded in female patients, with astatistically significant difference in the occurrence of gastrointestinaladverse effects and skin changes. Besides, gastrointestin al score wassignificantly higher i n p atients using MMF compared to EC MPS.Additionally, a relationship was established between C SAL andaesthetic score in patients with lower albumin levels.The obtained population pharmacokinetic model provides a basisforindividualized MPA dosing in pa tie nts with the presence of variabilityfactors. Gender differences should be taken into account whenoptimizing dosing regimens in order to achieve the efficacy and safetyof immunosuppressive therapy in kidney transplan t patients. Theresults showed that C S AL MPA monitoring may contribute tomanagement of adverse effects.

Description (srp)

Biografija autora: str. 144.Bibliografija: str. 97-139 Datum odbrane: 24.10.2023 Pharmacokinetic and clinical pharmacy

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