Population pharmacokinetic model to analyze nevirapine multiple-peaks profile after a single oral dose.
J Pharmacokinet Pharmacodyn
; 41(4): 363-73, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-25064169
ABSTRACT
Nevirapine (NVP) extensive data obtained after oral single dose administration of 200 mg in a crossover study involving 16 healthy subjects was used to develop a descriptive population pharmacokinetic model including drug recirculation, since secondary peaks were observed in plasma concentration-time profiles for all subjects. Through implementation of model event time feature in NONMEM 7.3.0, a simple mechanistic model physiologically consistent with the process of drug cycling was able to describe multiple peaks phenomena and quantify its pharmacokinetic parameters, achieving a better performance than its analogue conventional one. Absorption process, between subject and-between occasion variability of pharmacokinetic parameters was also assessed. Estimated mean fraction of NVP bioavailable dose undergoing recirculation process was 51.6 %, a magnitude which could hardly be explained by enterohepatic cycling. In this work we propose an alternative disposition process to explain NVP drug recirculation gastric secretion with posterior intestinal reabsorption. Due to physicochemical and pharmacokinetic properties of the drug, this neglected phenomenon is more likely to explain the results obtained, and might be present in disposition of several basic drugs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fármacos Anti-HIV
/
Nevirapina
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Pharmacokinet Pharmacodyn
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Uruguai