Pharmacokinetics and tissue distribution study of 10-methoxycamptothecin in rats following intragastric administration.
J Pharm Biomed Anal
; 149: 564-571, 2018 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-29197298
ABSTRACT
Natural bioactive derivatives of camptothecin (CPT), 10-methoxycamptothecin (MCPT) and 10-hydroxycamptothecin (HCPT) have been confirmed to possess high antitumor activities. MCPT could be metabolized to HCPT in vivo. The HPLC method for the quantification of MCPT and HCPT was established and validated, and the pharmacokinetics and the tissue distribution of MCPT in rats after i.v. administration have been well carried out in our previous studies. To improve the further understanding of the in vivo behavior of MCPT, a rapid and sensitive UPLC-MS/MS method was developed and validated for the quantification of MCPT and HCPT in plasma and tissue samples, and the pharmacokinetics and tissue distribution as well as the bioavailability of MCPT after i.g. were also illustrated. The results showed that MCPT could be highly converted to its active metabolite HCPT in plasma with the AUC0-∞ value of (185.28±61.73) ngh/mL and (717.25±165.67) ngh/mL for MCPT and HCPT, respectively. Meanwhile, MCPT and HCPT were rapidly absorbed and diffused into all the tested tissues (heart, liver, spleen, lung, kidney and brain) after i.g. administration. Similar with the results after i.v. administration of MCPT, MCPT concentration in lung tissue was also extremely higher than in other tested tissues, which implied that MCPT might have a great potential for the treatment of lung cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Camptotecina
/
Cromatografía Líquida de Alta Presión
/
Espectrometría de Masas en Tándem
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Pharm Biomed Anal
Año:
2018
Tipo del documento:
Article
País de afiliación:
China