Intravenous administration of irinotecan elevates the blood beta-glucuronidase activity in rats.
Cancer Res
; 57(23): 5305-8, 1997 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-9393754
ABSTRACT
7-Ethyl-10-hydroxycamptothecin (SN-38) is the active metabolite of an anticancer drug, irinotecan (CPT-11). Severe late diarrhea is the dose-limiting toxic effect of CPT-11. This diarrhea has been examined regarding biliary excretion and deconjugation of SN-38 glucuronide by the enzyme beta-glucuronidase (beta-GL) in intestinal microflora. Prompted by the enzymological and structural similarity of CPT-11 to organophosphorus and carbamate insecticides, we studied the effect of CPT-11 on blood beta-GL activity in rats. The i.v. injection of CPT-11 in rats significantly elevated their plasma beta-GL activity (with phenolphthalein glucuronide as a substrate) at doses of 10 and 40 mg/kg, with peak activity observed 2-3 h after administration. SN-38 lactone and carboxylate had no effect on the plasma beta-GL level. The enhancement of the activity was also observed in serum using SN-38 glucuronide as a substrate. The serum beta-GL levels showed a close correlation between these substrates. The enhancement of plasma (serum) beta-GL activity is suggested to be a result of the release of beta-GL from liver microsomes. Serum and microsomal carboxylesterase were not significantly affected by CPT-11 administration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
/
Hidrolases de Éster Carboxílico
/
Glucuronidase
/
Fígado
/
Antineoplásicos Fitogênicos
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Japão