Title
Farmakokinetička ispitivanja mikofenolne kiseline kod pacijenata sa presađenim bubregom
Creator
Kundalić, Ana A., 1988
CONOR:
108594953
Copyright date
2023
Object Links
Select license
Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
License description
Dozvoljavate samo preuzimanje i distribuciju dela, ako/dok se pravilno naznačava ime autora, bez ikakvih promena dela i bez prava komercijalnog korišćenja dela. Ova licenca je najstroža CC licenca. Osnovni opis Licence: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/deed.sr_LATN. Sadržaj ugovora u celini: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/legalcode.sr-Latn
Language
Serbian
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 24.10.2023
Other responsibilities
Alternative title
Pharmacokinetic analysis of mycophenolic acid in renal transplant recipients
Publisher
[A. A. Kundalić]
Format
147 str.
description
Biografija autora: str. 144.
Bibliografija: str. 97-139
description
Pharmacokinetic and clinical pharmacy
Abstract ()
Mycophenolic acid (MPA) is frequently prescribed as a part of
immuno suppressive protocols following kid ney transplantation.
Significant variability in MPA pharmacokinetics and the different
individual response emphasize the need for individualized dosing
regimens. The goals of this research were the development and
validat ion of HPLC method for the quantita tiv e analysis of MPA, the
identification of factors that contribute to the interindividual
variability of MPA, the assessment of the frequency and intensity of
adverse effects, the examine association of the salivary conc entration
(C SAL ) with the manifeste d a dverse effects, as well as the association
of the plasma and salivary concentration in relation to serum albumin
levels in kidney transplant patients.
This research included 102 adult kidney transplant patients. Plasma
and salivary MPA concentrations w ere determined by a validated
HPLC method and LC MS. The NONMEM® software was used for
the population analysis. The obtained model was further investigated
using Monte Carlo (MC) modeling. Adverse effects of the applied
t herapy were collected through a val ida ted questionnaire. A
correlation between plasma and salivary MPA concentrations was
established using the least squares method.
Population pharmacokinetic analysis identified patient age, MPA daily
dose, and nifedipine co therapy as significant factors in the variability
of MPA clearance. Using external validation method, the validity of
the obtained population model was confirmed. Furthermore, the
model was compared with similar models available in the literature
using the MC method, which confirmed its va lidity. A higher
frequency of adverse effects was recorded in female patients, with a
statistically significant difference in the occurrence of gastrointestinal
adverse effects and skin changes. Besides, gastrointestin al score was
significantly higher i n p atients using MMF compared to EC MPS.
Additionally, a relationship was established between C SAL and
aesthetic score in patients with lower albumin levels.
The obtained population pharmacokinetic model provides a basis
for
individualized MPA dosing in pa tie nts with the presence of variability
factors. Gender differences should be taken into account when
optimizing dosing regimens in order to achieve the efficacy and safety
of immunosuppressive therapy in kidney transplan t patients. The
results showed that C S AL MPA monitoring may contribute to
management of adverse effects.
Authors Key words
M
ikofenolna kiselina, validacija analitičke metode, populaciona
farmakokinetička analiza, neželjeni efekti, optimizacija terapije,
Monte Carlo modelovanje, presađi vanje bubrega
Authors Key words
Mycophenolic acid, ana
lytical method validation, populati on
pharmacokinetic analysis, adverse effects, therapy optimization,
Monte Carlo modeling, kidney transplantation
Classification
615.015:616.61-089.84(043.3)
Subject
B 740
Type
Tekst
Abstract ()
Mycophenolic acid (MPA) is frequently prescribed as a part of
immuno suppressive protocols following kid ney transplantation.
Significant variability in MPA pharmacokinetics and the different
individual response emphasize the need for individualized dosing
regimens. The goals of this research were the development and
validat ion of HPLC method for the quantita tiv e analysis of MPA, the
identification of factors that contribute to the interindividual
variability of MPA, the assessment of the frequency and intensity of
adverse effects, the examine association of the salivary conc entration
(C SAL ) with the manifeste d a dverse effects, as well as the association
of the plasma and salivary concentration in relation to serum albumin
levels in kidney transplant patients.
This research included 102 adult kidney transplant patients. Plasma
and salivary MPA concentrations w ere determined by a validated
HPLC method and LC MS. The NONMEM® software was used for
the population analysis. The obtained model was further investigated
using Monte Carlo (MC) modeling. Adverse effects of the applied
t herapy were collected through a val ida ted questionnaire. A
correlation between plasma and salivary MPA concentrations was
established using the least squares method.
Population pharmacokinetic analysis identified patient age, MPA daily
dose, and nifedipine co therapy as significant factors in the variability
of MPA clearance. Using external validation method, the validity of
the obtained population model was confirmed. Furthermore, the
model was compared with similar models available in the literature
using the MC method, which confirmed its va lidity. A higher
frequency of adverse effects was recorded in female patients, with a
statistically significant difference in the occurrence of gastrointestinal
adverse effects and skin changes. Besides, gastrointestin al score was
significantly higher i n p atients using MMF compared to EC MPS.
Additionally, a relationship was established between C SAL and
aesthetic score in patients with lower albumin levels.
The obtained population pharmacokinetic model provides a basis
for
individualized MPA dosing in pa tie nts with the presence of variability
factors. Gender differences should be taken into account when
optimizing dosing regimens in order to achieve the efficacy and safety
of immunosuppressive therapy in kidney transplan t patients. The
results showed that C S AL MPA monitoring may contribute to
management of adverse effects.
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