Plasma protein distribution and its impact on pharmacokinetics of liposomal amphotericin B in paediatric patients with malignant diseases.
Eur J Clin Pharmacol
; 63(2): 165-72, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17180621
ABSTRACT
OBJECTIVE:
This study investigates the association of liposomal amphotericin B (L-AmB) with plasma proteins and its impact on the pharmacokinetics of L-AmB in paediatric patients with malignant diseases.METHODS:
Paediatric oncology patients (n = 39) who received multiple-doses of L-AmB were recruited into this study. The association of the drug with plasma lipoprotein was investigated using single vertical spin density gradient ultracentrifugation and quantitated with a validated HPLC assay. The unbound amphotericin B (AmB) in the plasma was separated by ultrafiltration and determined with a validated LC/MS/MS assay.RESULTS:
The ex vivo lipoprotein distribution of L-AmB found that 68.3 +/- 11.8% of the drug was associated with the high density lipoprotein (HDL) fraction, which demonstrated a significant inverse correlation with posterior Bayesian estimates of L-AmB clearance (r = -0.690, p < 0.01). The average of unbound fraction of AmB in plasma of patients administered with L-AmB was 0.005, but its relationship with L-AmB clearance did not reach a statistical significance.CONCLUSION:
L-AmB displays different lipoprotein distribution profile from that of the conventional AmB formulation, with L-AmB preferentially associated with HDL in plasma. The inverse correlation of L-AmB clearance to its HDL distribution contributes to the difference in the pharmacokinetic profile of L-AmB.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anfotericina B
/
Lipoproteínas
/
Antifúngicos
/
Neoplasias
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Austrália