Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling
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2013
Authors
Jovanović, Marija
Sokić, Dragoslav
Grabnar, Iztok

Vovk, Tomaz
Prostran, Milica

Vučićević, Katarina

Miljković, Branislava

Article (Published version)

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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 / NONMEMSource:
European Journal of Pharmaceutical Sciences, 2013, 50, 3-4, 282-289Publisher:
- Elsevier Science BV, Amsterdam
Funding / projects:
DOI: 10.1016/j.ejps.2013.07.008
ISSN: 0928-0987
PubMed: 23891703
WoS: 000325838800005
Scopus: 2-s2.0-84884528877
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PharmacyTY - 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 . .