Quantitative drug benefit-risk assessment: utility of modeling and simulation to optimize drug safety in older adults.
Ann Pharmacother
; 48(3): 306-13, 2014 Mar.
Article
en En
| MEDLINE
| ID: mdl-24473487
ABSTRACT
BACKGROUND:
More than 50 % of individuals affected by adverse drug events (ADEs) are older adults. Establishing a drug dosing regimen that balances benefit and risk, and minimizes ADEs in older populations can be challenging.OBJECTIVE:
The aim of this study is to evaluate the use of modeling, simulation, and risk-benefit acceptability methods to establish a drug dosing regimen that balances benefit and risk.METHODS:
The study population comprised nondiabetic patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) ≥50 years old, who had been on oral olanzapine for ≥2 weeks. We used mixed-effects modeling based on a preexisting pharmacokinetic model to derive clearance estimates, which were then used to determine the olanzapine area under the concentration-time curve (AUC). Subsequently, with multivariate regression and Monte Carlo simulation, we estimated the olanzapine dose corresponding to the benefit-risk AUC breakpoint.RESULTS:
The study population (n = 34) was predominantly male (82.3%) and white (67.6%), with a mean age of 54.4 years and treatment duration of 361.8 days. The mean AUC was 747.6 ng h/mL (95% CI = 524.5, 970.7) for the benefit group (n = 16) and 754.1 (95% CI = 505.9, 1002.4) for the risk group (n = 15). The benefit-risk AUC breakpoint was 524.5 ng h/mL and the corresponding oral olanzapine dose that optimizes benefit-risk balance was 17.8 mg/d.CONCLUSIONS:
Our study introduces a real-world approach for finding the safe drug dosing regimen without extensive exposure of a vulnerable and older population to drugs. Further studies into the use of modeling, simulation, and risk-benefit acceptability methods to enhance geriatric drug safety are needed.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Esquizofrenia
/
Antipsicóticos
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Benzodiazepinas
/
Medición de Riesgo
/
Modelos Biológicos
Tipo de estudio:
Etiology_studies
/
Health_economic_evaluation
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Ann Pharmacother
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos