Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations
<b>Background/Objectives:</b> Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a populatio...
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2024-11-01
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| author | Firas Al-Zubaydi Andrew Wassef Leonid Kagan Luigi Brunetti |
| author_facet | Firas Al-Zubaydi Andrew Wassef Leonid Kagan Luigi Brunetti |
| author_sort | Firas Al-Zubaydi |
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| description | <b>Background/Objectives:</b> Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a population PK (popPK) model and characterize significant covariates that impact gabapentin PK. <b>Methods:</b> Data were retrospectively collected from 82 hospitalized adult patients with TDM gabapentin concentrations. Renal function indicators (i.e., estimated glomerular filtration rate, creatinine clearance, acute kidney injury), body weight parameters (i.e., actual body weight, ideal body weight, adjusted body weight, lean body weight, body mass index, obesity status), fasting plasma glucose levels, and diagnosis of type 2 diabetes were tested as potential covariates. A popPK model was developed in MONOLIX (2020R1, Lixoft, France). <b>Results</b>: A one-compartment model best described gabapentin PK with first-order absorption, dose-dependent bioavailability, first-order elimination, and no lag time. Population parameter estimates for the volume of distribution (V<sub>d</sub>), and clearance (Cl) were 44.61 L, and 5.73 L/h, respectively. Serum creatinine was a significant covariate on Cl. <b>Conclusions</b>: The popPK model highlights the importance of renal function in the interindividual variability of gabapentin PK and suggests that diabetes and body weight parameters have no impact on gabapentin PK. Moreover, our study supports the utility of leveraging data obtained from clinical TDM for popPK model development. |
| format | Article |
| id | doaj-art-14a27f5164cc49d8b0e0930592bd2c0d |
| institution | Kabale University |
| issn | 1999-4923 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-14a27f5164cc49d8b0e0930592bd2c0d2024-12-27T14:46:21ZengMDPI AGPharmaceutics1999-49232024-11-011612151410.3390/pharmaceutics16121514Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring ConcentrationsFiras Al-Zubaydi0Andrew Wassef1Leonid Kagan2Luigi Brunetti3Department of Pharmacy Practice, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USADepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USADepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USADepartment of Pharmacy Practice, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA<b>Background/Objectives:</b> Gabapentin has variable pharmacokinetics (PK), which contributes to difficulty in dosing and increased risk of adverse events. The objective of this study was to leverage gabapentin concentrations from therapeutic drug monitoring (TDM) to develop a population PK (popPK) model and characterize significant covariates that impact gabapentin PK. <b>Methods:</b> Data were retrospectively collected from 82 hospitalized adult patients with TDM gabapentin concentrations. Renal function indicators (i.e., estimated glomerular filtration rate, creatinine clearance, acute kidney injury), body weight parameters (i.e., actual body weight, ideal body weight, adjusted body weight, lean body weight, body mass index, obesity status), fasting plasma glucose levels, and diagnosis of type 2 diabetes were tested as potential covariates. A popPK model was developed in MONOLIX (2020R1, Lixoft, France). <b>Results</b>: A one-compartment model best described gabapentin PK with first-order absorption, dose-dependent bioavailability, first-order elimination, and no lag time. Population parameter estimates for the volume of distribution (V<sub>d</sub>), and clearance (Cl) were 44.61 L, and 5.73 L/h, respectively. Serum creatinine was a significant covariate on Cl. <b>Conclusions</b>: The popPK model highlights the importance of renal function in the interindividual variability of gabapentin PK and suggests that diabetes and body weight parameters have no impact on gabapentin PK. Moreover, our study supports the utility of leveraging data obtained from clinical TDM for popPK model development.https://www.mdpi.com/1999-4923/16/12/1514gabapentingamma-aminobutyric acidpopulation pharmacokineticstherapeutic drug monitoringcreatinine |
| spellingShingle | Firas Al-Zubaydi Andrew Wassef Leonid Kagan Luigi Brunetti Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations Pharmaceutics gabapentin gamma-aminobutyric acid population pharmacokinetics therapeutic drug monitoring creatinine |
| title | Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations |
| title_full | Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations |
| title_fullStr | Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations |
| title_full_unstemmed | Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations |
| title_short | Development of a Population Pharmacokinetic Gabapentin Model Leveraging Therapeutic Drug Monitoring Concentrations |
| title_sort | development of a population pharmacokinetic gabapentin model leveraging therapeutic drug monitoring concentrations |
| topic | gabapentin gamma-aminobutyric acid population pharmacokinetics therapeutic drug monitoring creatinine |
| url | https://www.mdpi.com/1999-4923/16/12/1514 |
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