Prediction of the pharmacokinetics of pemetrexed with a low test dose: A proof-of-concept study.
Br J Clin Pharmacol
; 89(2): 699-704, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36053283
ABSTRACT
PURPOSE:
Pemetrexed is a cytotoxic drug used for the treatment of lung cancer and mesothelioma. The use of a low test dosing of cytotoxic drugs may aid in dose individualization without causing harm. The aim of this proof-of-concept study was to assess if the pharmacokinetics (PKs) of a test dose could predict the PKs of a therapeutic pemetrexed dose.METHODS:
Ten patients received both a low test dose (100 µg) and a therapeutic dose of pemetrexed after which plasma concentrations pemetrexed were measured. PK analysis was performed by means of nonlinear mixed-effects modelling. The predictive performances of test dose clearance and renal function towards a therapeutic dose were assessed.RESULTS:
The PKs of a pemetrexed test dose were best described by a one-compartment model with linear elimination. A high variability in the administered dose was observed for the test dose, but not for the therapeutic dose. A statistically significant correlation between test dose clearance and therapeutic dose clearance was observed (Spearman's rho 0.758, P = 0.02). The predictive performance of test dose clearance was worse than renal function mean predictive error (+95% confidence interval [CI]) 53.9% (50.1-57.6%) vs 19.4% (12.4-26.4%) and normalized root-mean square error (+95% CI) 57.8% (30.5-85.1%) vs 25.7% (20.3-31.0%).CONCLUSION:
We show that test dosing of pemetrexed is feasible, but there seems no added value for a low test dosing in the dose individualization of pemetrexed.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pulmonares
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda