Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients
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2015
Authors
Vučićević, Katarina
Jovanović, Marija

Golubović, Bojana
Vezmar-Kovačević, Sandra

Miljković, Branislava

Martinović, Žarko J.
Prostran, Milica

Article (Published version)

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The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients. In total 205 PB concentrations were obtained during routine clinical monitoring of 136 adult epilepsy patients. PB steady state concentrations were measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling (NONMEM) was applied for data analyses and evaluation of the final model. According to the final population model, significant determinant of apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 % decre...ase in PB CL/F. Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA.
Keywords:
Phenobarbital / Interactions / Pharmacokinetics / Therapeutic drug monitoring / NONMEMSource:
European Journal of Clinical Pharmacology, 2015, 71, 2, 183-190Publisher:
- Springer Heidelberg, Heidelberg
Funding / projects:
DOI: 10.1007/s00228-014-1778-7
ISSN: 0031-6970
PubMed: 25380628
WoS: 000348148200007
Scopus: 2-s2.0-84922074826
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PharmacyTY - JOUR AU - Vučićević, Katarina AU - Jovanović, Marija AU - Golubović, Bojana AU - Vezmar-Kovačević, Sandra AU - Miljković, Branislava AU - Martinović, Žarko J. AU - Prostran, Milica PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2408 AB - The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients. In total 205 PB concentrations were obtained during routine clinical monitoring of 136 adult epilepsy patients. PB steady state concentrations were measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling (NONMEM) was applied for data analyses and evaluation of the final model. According to the final population model, significant determinant of apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 % decrease in PB CL/F. Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA. PB - Springer Heidelberg, Heidelberg T2 - European Journal of Clinical Pharmacology T1 - Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients VL - 71 IS - 2 SP - 183 EP - 190 DO - 10.1007/s00228-014-1778-7 ER -
@article{ author = "Vučićević, Katarina and Jovanović, Marija and Golubović, Bojana and Vezmar-Kovačević, Sandra and Miljković, Branislava and Martinović, Žarko J. and Prostran, Milica", year = "2015", abstract = "The present study aimed to establish population pharmacokinetic model for phenobarbital (PB), examining and quantifying the magnitude of PB interactions with other antiepileptic drugs concomitantly used and to demonstrate its use for individualization of PB dosing regimen in adult epileptic patients. In total 205 PB concentrations were obtained during routine clinical monitoring of 136 adult epilepsy patients. PB steady state concentrations were measured by homogeneous enzyme immunoassay. Nonlinear mixed effects modelling (NONMEM) was applied for data analyses and evaluation of the final model. According to the final population model, significant determinant of apparent PB clearance (CL/F) was daily dose of concomitantly given valproic acid (VPA). Typical value of PB CL/F for final model was estimated at 0.314 l/h. Based on the final model, co-therapy with usual VPA dose of 1000 mg/day, resulted in PB CL/F average decrease of about 25 %, while 2000 mg/day leads to an average 50 % decrease in PB CL/F. Developed population PB model may be used in estimating individual CL/F for adult epileptic patients and could be applied for individualizing dosing regimen taking into account dose-dependent effect of concomitantly given VPA.", publisher = "Springer Heidelberg, Heidelberg", journal = "European Journal of Clinical Pharmacology", title = "Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients", volume = "71", number = "2", pages = "183-190", doi = "10.1007/s00228-014-1778-7" }
Vučićević, K., Jovanović, M., Golubović, B., Vezmar-Kovačević, S., Miljković, B., Martinović, Ž. J.,& Prostran, M.. (2015). Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. in European Journal of Clinical Pharmacology Springer Heidelberg, Heidelberg., 71(2), 183-190. https://doi.org/10.1007/s00228-014-1778-7
Vučićević K, Jovanović M, Golubović B, Vezmar-Kovačević S, Miljković B, Martinović ŽJ, Prostran M. Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients. in European Journal of Clinical Pharmacology. 2015;71(2):183-190. doi:10.1007/s00228-014-1778-7 .
Vučićević, Katarina, Jovanović, Marija, Golubović, Bojana, Vezmar-Kovačević, Sandra, Miljković, Branislava, Martinović, Žarko J., Prostran, Milica, "Nonlinear mixed effects modelling approach in investigating phenobarbital pharmacokinetic interactions in epileptic patients" in European Journal of Clinical Pharmacology, 71, no. 2 (2015):183-190, https://doi.org/10.1007/s00228-014-1778-7 . .