Population pharmacokinetics of free and liposome-encapsulated mitoxantrone in patients with relapsed/refractory lymphoma or small cell lung cancer.
Eur J Clin Pharmacol
; 80(9): 1399-1407, 2024 Sep.
Article
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| MEDLINE
| ID: mdl-38904799
ABSTRACT
OBJECTIVE:
This study is aimed at investigating the pharmacokinetic (PK) characteristics of pegylated liposomal mitoxantrone (PLM) in patients with relapsed/refractory lymphoma or small cell lung cancer (SCLC) by constructing population pharmacokinetic (popPK) models for both liposome-encapsulated mitoxantrone and free mitoxantrone.METHODS:
A total of 23 patients with relapsed/refractory lymphoma and 42 patients with SCLC were included. A popPK model was simultaneously developed utilizing a non-linear mixed effects model (NONMEM) to explore the PK profiles of liposome-encapsulated mitoxantrone and free mitoxantrone. Clearance (CL) and distribution volume (V) were calculated, and covariate analysis was employed to evaluate the influence of patient disease type, demographic information, and biochemical indicators of liver and kidney function on PK parameters.RESULTS:
The concentration-time profiles for both liposome-encapsulated mitoxantrone and free mitoxantrone were described by a one-compartment model. The release (Rel) of liposome-encapsulated mitoxantrone to free mitoxantrone was determined to be 0.0191 L/h, and the V of liposome-encapsulated mitoxantrone was 2.32 L. The apparent CL of free mitoxantrone was estimated at 1.66 L/h. The apparent V of free mitoxantrone was 35.8 L in patients with relapsed/refractory lymphoma and 22.2 L for patients with SCLC. In patients with relapsed/refractory lymphoma, lower maximum concentration (Cmax) and higher apparent V of free mitoxantrone were observed compared with patients with SCLC.CONCLUSION:
The popPK characteristics of both liposome-encapsulated and free mitoxantrone in patients with relapsed/refractory lymphoma or SCLC were effectively described by a one-compartment model.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mitoxantrona
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Carcinoma Pulmonar de Células Pequeñas
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Liposomas
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Neoplasias Pulmonares
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Modelos Biológicos
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China