Aluminum toxicokinetics in peritoneal dialysis patients.
Clin Toxicol (Phila)
; 49(7): 659-63, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21819285
ABSTRACT
CONTEXT Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition. METHODS:
Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion.RESULTS:
After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues.CONCLUSION:
This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Soluções para Diálise
/
Contaminação de Medicamentos
/
Diálise Peritoneal
/
Alumínio
/
Nefropatias
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Clin Toxicol (Phila)
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Canadá