New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen
Abstract
:1. Introduction
2. Materials and Methods
2.1. Literature Data Collection
2.2. Population Pharmacokinetic Modelling
2.3. Model Evaluation and Validation
2.4. Monte Carlo Simulation and Optimization of NEB Dose Regimen
3. Results
3.1. Collection of the Literature Data
3.2. Subject Characteristics
3.3. Model Building Process
3.4. Model Evaluation
3.5. Dose Regimen Optimization
3.5.1. Multiple-Dose Treatment of 2.5 mg
3.5.2. Proposed Treatment of 6 mg
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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No. Treatment | Dose Regimen for NEB |
---|---|
1 | 5 mg once a day for 15 days |
2 | 10 mg once a day for 15 days |
3 | 20 mg once a day for 15 days |
4 | 2.5 mg once a day for 15 days |
5 * | 2.5 mg BID for 15 days |
6 * | 2.5 mg q6 h for 15 days |
7 * | 6 mg q36 h for 15 days |
8 * | 6 mg q48 h for 15 days |
Study Number | Reference | Studied Population | NEB Doses | Period of Treatments | Number of Individuals Generated |
---|---|---|---|---|---|
1 | [9] | Healthy adults (n = 30) | 20 mg | Oral daily dose for 27 days | 1 |
2 | [10] | Healthy adults (n = 23) | 5 mg | Single oral dose | 1 |
3 | [11] | Healthy adults (n = 43) | 5 mg | Single oral dose | 2 |
4 | [12] | Healthy adults (n = 18) | 5 mg | Single oral dose | 1 |
5 | [13] | Healthy adults (n = 18) | 5 mg | Single oral dose | 1 |
6 | [14] | Healthy adults (n = 24) | 10 mg | Single oral dose | 24 |
Total | 30 |
Parameter | NEB (n = 30) |
---|---|
Age (years) | 26.70 ± 1.40 (20–34 years) |
Body-mass index (kg/m2) | 25.00 ± 1.00 |
Genotype (n, %) | |
Extensive Metabolizers (EMs) | 17, 56.7 |
Intermediate Metabolizers (IMs) | 12, 40 |
Poor Metabolizers (PMs) | 1, 3.3 |
Ethnic (n, %) | |
Caucasian | 6, 20 |
Asian | 24, 80 |
Parameter | Mean | RSE (%) |
---|---|---|
5 mg | ||
Cmax (ng·mL−1) | 2.40 | 0.78 |
AUC (ng·h·mL−1) | 37.29 | 1.09 |
Tmax (h) | 1.66 | 18.77 |
Kel (L/h) | 0.17 | 0.16 |
t1/2 (h) | 6.92 | 5.31 |
10 mg | ||
Cmax (ng·mL−1) | 2.65 | ND |
AUC (ng·h·mL−1) | 1.51 | ND |
Tmax (h) | 21.56 | ND |
Kel (L/h) | 2.72 | ND |
t1/2 (h) | 12.52 | ND |
20 mg | ||
Cmax (ng·mL−1) | 8.02 | 3.47 |
AUC (ng·h·mL−1) | 41.50 | 0.67 |
Tmax (h) | 1.32 | 29.76 |
Kel (L/h) | ND | ND |
t1/2 (h) | 11.03 | 2.12 |
Parameter | Estimate | RSE (%) |
---|---|---|
Tlag pop | 0.30 | 10.8 |
Ka pop | 2.06 | 10.4 |
Cl pop | 0.22 | 36.7 |
V1 pop | 4.21 | 4.96 |
Q pop | 0.59 | 5.73 |
V2 pop | 7.12 | 11.2 |
Error model parameters | ||
b | 0.13 | 4.63 |
Target | 2.5 mg | 5 mg | 10 mg | 20 mg |
---|---|---|---|---|
Efficacy Target | 1% | 72.2% | 22.6% | 0.5% |
Safety Target | 97% | 95.5% | 69.6% | 19.1% |
Target | 2.5 mg BID | 2.5 mg q6 h | 6 mg q36 h | 6 mg q48 h |
---|---|---|---|---|
Efficacy Target | 0.9% | 0% | 75.2% | 72.6% |
Safety Target | 99.1% | 100% | 97% | 96.7% |
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Marques, L.; Costa, B.; Vale, N. New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen. Pharmaceutics 2022, 14, 1911. https://doi.org/10.3390/pharmaceutics14091911
Marques L, Costa B, Vale N. New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen. Pharmaceutics. 2022; 14(9):1911. https://doi.org/10.3390/pharmaceutics14091911
Chicago/Turabian StyleMarques, Lara, Bárbara Costa, and Nuno Vale. 2022. "New Data for Nebivolol after In Silico PK Study: Focus on Young Patients and Dosage Regimen" Pharmaceutics 14, no. 9: 1911. https://doi.org/10.3390/pharmaceutics14091911