Pre-clinical compartmental pharmacokinetic modeling of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) as a photosensitizer in rat plasma by validated HPLC method.
Photochem Photobiol Sci
; 18(5): 1056-1063, 2019 May 15.
Article
em En
| MEDLINE
| ID: mdl-30608096
ABSTRACT
A second-generation chlorin-based photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) has shown tremendous therapeutic potential in clinical trials in the treatment of esophageal cancer. Herein, we have developed and validated a bioanalytical method for estimation of HPPH in rat plasma using High Performance Liquid Chromatography (HPLC) with a photo diode array (PDA) detector. The method was applied for carrying out pharmacokinetic study of HPPH. Further pharmacokinetic modeling was carried out to understand the compartment kinetics of HPPH. The developed method was fully validated as per the United States Food and Drug Administration (US-FDA) guidelines for bioanalytical method validation. The linearity of the method was in the range of 250-8000 ng mL-1, and the plasma recovery was found to be 70%. Pharmacokinetic parameters were evaluated and compared via non-compartment analysis and compartment modeling after the intravenous (i.v.) bolus administration in rats using Phoenix WinNonlin 8.0 (Certara™, USA). From the obtained results, we hypothesize that the HPPH complies with two compartmental pharmacokinetic model. Furthermore, it was observed that HPPH has the rapid distribution from the central compartment to peripheral compartment along with slow elimination from peripheral compartment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clorofila
/
Fármacos Fotossensibilizantes
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Photochem Photobiol Sci
Assunto da revista:
BIOLOGIA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia