Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients
(1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected fr...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/4/811 |
| _version_ | 1797409645824835584 |
|---|---|
| author | Paulo Teixeira-da-Silva Jonás Samuel Pérez-Blanco Dolores Santos-Buelga María José Otero María José García |
| author_facet | Paulo Teixeira-da-Silva Jonás Samuel Pérez-Blanco Dolores Santos-Buelga María José Otero María José García |
| author_sort | Paulo Teixeira-da-Silva |
| collection | DOAJ |
| description | (1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected from 1204 patients included in a therapeutic drug monitoring program were retrospectively analyzed. Patients were randomly assigned to either a model development group or an external evaluation group. PopPK analysis was performed on 1751 samples from 776 patients with NONMEM using a nonlinear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment and comedication variables on the apparent clearance (CL/F) of VPA was studied. The bootstrap method was used to evaluate the final model internally. External evaluation was carried out using 776 VPA serum samples from 368 patients. (3) Results: A one-compartment model with first-order absorption and elimination successfully described the data. The final model included total body weight, age and comedication with phenytoin, phenobarbital and carbamazepine with a significant impact on VPA elimination. Internal and external evaluations demonstrated the good predictability of the model. (4) Conclusions: A PopPK model of VPA in Caucasian patients was successfully established, which will be helpful for model-informed precision dosing approaches in clinical patient care. |
| first_indexed | 2024-03-09T04:17:34Z |
| format | Article |
| id | doaj.art-003e61eef49a486dac1edaf3a5b524a7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T04:17:34Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-003e61eef49a486dac1edaf3a5b524a72023-12-03T13:50:37ZengMDPI AGPharmaceutics1999-49232022-04-0114481110.3390/pharmaceutics14040811Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian PatientsPaulo Teixeira-da-Silva0Jonás Samuel Pérez-Blanco1Dolores Santos-Buelga2María José Otero3María José García4Pharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, SpainPharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, SpainPharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, SpainInstitute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, SpainPharmaceutical Sciences Department, Universidad de Salamanca, 37007 Salamanca, Spain(1) Background: The aim of this study was to explore the valproic acid (VPA) pharmacokinetic characteristics in a large population of pediatric and adult Caucasian patients and to establish a robust population pharmacokinetic (PopPK) model. (2) Methods: A total of 2527 serum VPA samples collected from 1204 patients included in a therapeutic drug monitoring program were retrospectively analyzed. Patients were randomly assigned to either a model development group or an external evaluation group. PopPK analysis was performed on 1751 samples from 776 patients with NONMEM using a nonlinear mixed-effect modelling approach. The influence of demographic, anthropometric, treatment and comedication variables on the apparent clearance (CL/F) of VPA was studied. The bootstrap method was used to evaluate the final model internally. External evaluation was carried out using 776 VPA serum samples from 368 patients. (3) Results: A one-compartment model with first-order absorption and elimination successfully described the data. The final model included total body weight, age and comedication with phenytoin, phenobarbital and carbamazepine with a significant impact on VPA elimination. Internal and external evaluations demonstrated the good predictability of the model. (4) Conclusions: A PopPK model of VPA in Caucasian patients was successfully established, which will be helpful for model-informed precision dosing approaches in clinical patient care.https://www.mdpi.com/1999-4923/14/4/811drug interactionstherapeutic drug monitoringepilepsyNONMEMpopulation pharmacokineticsvalproic acid |
| spellingShingle | Paulo Teixeira-da-Silva Jonás Samuel Pérez-Blanco Dolores Santos-Buelga María José Otero María José García Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients Pharmaceutics drug interactions therapeutic drug monitoring epilepsy NONMEM population pharmacokinetics valproic acid |
| title | Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients |
| title_full | Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients |
| title_fullStr | Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients |
| title_full_unstemmed | Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients |
| title_short | Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients |
| title_sort | population pharmacokinetics of valproic acid in pediatric and adult caucasian patients |
| topic | drug interactions therapeutic drug monitoring epilepsy NONMEM population pharmacokinetics valproic acid |
| url | https://www.mdpi.com/1999-4923/14/4/811 |
| work_keys_str_mv | AT pauloteixeiradasilva populationpharmacokineticsofvalproicacidinpediatricandadultcaucasianpatients AT jonassamuelperezblanco populationpharmacokineticsofvalproicacidinpediatricandadultcaucasianpatients AT doloressantosbuelga populationpharmacokineticsofvalproicacidinpediatricandadultcaucasianpatients AT mariajoseotero populationpharmacokineticsofvalproicacidinpediatricandadultcaucasianpatients AT mariajosegarcia populationpharmacokineticsofvalproicacidinpediatricandadultcaucasianpatients |