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Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling

Authorized Users Only
2013
Authors
Jovanović, Marija
Sokić, Dragoslav
Grabnar, Iztok
Vovk, Tomaz
Prostran, Milica
Vučićević, Katarina
Miljković, Branislava
Article (Published version)
Metadata
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Abstract
The objective of the study was to develop population pharmacokinetic model of topiramate (TPM) using nonlinear mixed effects modelling approach. Data were collected from 78 adult epileptic patients on mono- or co-therapy of TPM and other antiepileptic drugs, such as carbamazepine (CBZ), valproic acid, lamotrigine, levetiracetam, phenobarbital and pregabalin. Steady-state TPM concentrations were determined in blood samples by high performance liquid chromatography with fluorescence detection. A one-compartment model with first order absorption and elimination was used to fit the concentration-time TPM data. Volume of distribution of TPM was estimated at 0.575 l/kg. The influence of demographic, biochemical parameters and therapy characteristics of the patients on oral clearance (CL/F) was evaluated. Daily carbamazepine dose (DCBZ) and renal function estimated by Modification of diet in renal disease (MDRD) formula significantly (p lt 0.001) influenced CL/F and were included in the fin...al model: CL/F . (l/h) = 1.53(1/h) . [1 + 0.476 . DCBZ(mg/day)/1000(mg/day)] . EXP[0.00476 . [MDRD(ml/min) -95.72(ml/ mm)]]. Increase of CL/F with DCBZ and MDRD was best described by linear and exponential models. Mean TPM CL/F during CBZ co-therapy was 2.46 l/h, which is higher for 60.8% than in patients not co-treated with CBZ. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by adequate plots and indicated satisfactory precision. This model allows individualisation of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimen.

Keywords:
Topiramate / Carbamazepine / Renal function / Population pharmacokinetics / NONMEM
Source:
European Journal of Pharmaceutical Sciences, 2013, 50, 3-4, 282-289
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Basic and Clinical Pharmacological research of mechanisms of action and drug interactions in nervous and cardiovascular system (RS-175023)

DOI: 10.1016/j.ejps.2013.07.008

ISSN: 0928-0987

PubMed: 23891703

WoS: 000325838800005

Scopus: 2-s2.0-84884528877
[ Google Scholar ]
12
12
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1844
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Jovanović, Marija
AU  - Sokić, Dragoslav
AU  - Grabnar, Iztok
AU  - Vovk, Tomaz
AU  - Prostran, Milica
AU  - Vučićević, Katarina
AU  - Miljković, Branislava
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1844
AB  - The objective of the study was to develop population pharmacokinetic model of topiramate (TPM) using nonlinear mixed effects modelling approach. Data were collected from 78 adult epileptic patients on mono- or co-therapy of TPM and other antiepileptic drugs, such as carbamazepine (CBZ), valproic acid, lamotrigine, levetiracetam, phenobarbital and pregabalin. Steady-state TPM concentrations were determined in blood samples by high performance liquid chromatography with fluorescence detection. A one-compartment model with first order absorption and elimination was used to fit the concentration-time TPM data. Volume of distribution of TPM was estimated at 0.575 l/kg. The influence of demographic, biochemical parameters and therapy characteristics of the patients on oral clearance (CL/F) was evaluated. Daily carbamazepine dose (DCBZ) and renal function estimated by Modification of diet in renal disease (MDRD) formula significantly (p  lt  0.001) influenced CL/F and were included in the final model: CL/F . (l/h) = 1.53(1/h) . [1 + 0.476 . DCBZ(mg/day)/1000(mg/day)] . EXP[0.00476 . [MDRD(ml/min) -95.72(ml/ mm)]]. Increase of CL/F with DCBZ and MDRD was best described by linear and exponential models. Mean TPM CL/F during CBZ co-therapy was 2.46 l/h, which is higher for 60.8% than in patients not co-treated with CBZ. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by adequate plots and indicated satisfactory precision. This model allows individualisation of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimen.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmaceutical Sciences
T1  - Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling
VL  - 50
IS  - 3-4
SP  - 282
EP  - 289
DO  - 10.1016/j.ejps.2013.07.008
ER  - 
@article{
author = "Jovanović, Marija and Sokić, Dragoslav and Grabnar, Iztok and Vovk, Tomaz and Prostran, Milica and Vučićević, Katarina and Miljković, Branislava",
year = "2013",
abstract = "The objective of the study was to develop population pharmacokinetic model of topiramate (TPM) using nonlinear mixed effects modelling approach. Data were collected from 78 adult epileptic patients on mono- or co-therapy of TPM and other antiepileptic drugs, such as carbamazepine (CBZ), valproic acid, lamotrigine, levetiracetam, phenobarbital and pregabalin. Steady-state TPM concentrations were determined in blood samples by high performance liquid chromatography with fluorescence detection. A one-compartment model with first order absorption and elimination was used to fit the concentration-time TPM data. Volume of distribution of TPM was estimated at 0.575 l/kg. The influence of demographic, biochemical parameters and therapy characteristics of the patients on oral clearance (CL/F) was evaluated. Daily carbamazepine dose (DCBZ) and renal function estimated by Modification of diet in renal disease (MDRD) formula significantly (p  lt  0.001) influenced CL/F and were included in the final model: CL/F . (l/h) = 1.53(1/h) . [1 + 0.476 . DCBZ(mg/day)/1000(mg/day)] . EXP[0.00476 . [MDRD(ml/min) -95.72(ml/ mm)]]. Increase of CL/F with DCBZ and MDRD was best described by linear and exponential models. Mean TPM CL/F during CBZ co-therapy was 2.46 l/h, which is higher for 60.8% than in patients not co-treated with CBZ. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by adequate plots and indicated satisfactory precision. This model allows individualisation of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimen.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmaceutical Sciences",
title = "Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling",
volume = "50",
number = "3-4",
pages = "282-289",
doi = "10.1016/j.ejps.2013.07.008"
}
Jovanović, M., Sokić, D., Grabnar, I., Vovk, T., Prostran, M., Vučićević, K.,& Miljković, B.. (2013). Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling. in European Journal of Pharmaceutical Sciences
Elsevier Science BV, Amsterdam., 50(3-4), 282-289.
https://doi.org/10.1016/j.ejps.2013.07.008
Jovanović M, Sokić D, Grabnar I, Vovk T, Prostran M, Vučićević K, Miljković B. Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling. in European Journal of Pharmaceutical Sciences. 2013;50(3-4):282-289.
doi:10.1016/j.ejps.2013.07.008 .
Jovanović, Marija, Sokić, Dragoslav, Grabnar, Iztok, Vovk, Tomaz, Prostran, Milica, Vučićević, Katarina, Miljković, Branislava, "Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling" in European Journal of Pharmaceutical Sciences, 50, no. 3-4 (2013):282-289,
https://doi.org/10.1016/j.ejps.2013.07.008 . .

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