Opiate effects on 5-fluorouracil disposition in mice.
Cancer Chemother Pharmacol
; 39(3): 273-7, 1997.
Article
em En
| MEDLINE
| ID: mdl-8996532
ABSTRACT
PURPOSE:
This study was performed to investigate the effects of morphine on the disposition of 5-fluorouracil (5-FU).METHODS:
Mice were injected subcutaneously (s.c.) with saline or morphine, 20 mg/kg. 5-FU was administered intravenously (i.v.) 30 min later as a single bolus or by constant infusion. Blood samples were obtained by orbital sinus puncture. Urine samples were obtained from the bladder after ligation of the external urethra. 5-FU concentrations in plasma and urine were determined by HPLC.RESULTS:
Morphine markedly elevated plasma levels of 5-FU given at doses of 100 to 860 mg/kg. The plasma clearance rate of a bolus dose of 100 mg/kg 5-FU was significantly reduced from 54 to 28 ml/min per kg and the elimination half-life was increased from 6.9 to 12.2 min by prior administration of morphine. When 5-FU was infused at 0.5 mg/kg per min, morphine reduced its plasma clearance rate from 145 to 94 ml/min per kg. Mice made tolerant by prior morphine administration required higher doses of this opiate to raise 5-FU levels as well as to cause analgesia. The effects of morphine on 5-FU disposition were antagonized by naltrexone. Excretion of 5-FU in urine was not affected by morphine treatment.CONCLUSIONS:
The plasma clearance rate of 5-FU in mice is significantly reduced by concomitant use of morphine. This effect of morphine is due to reduced hepatic elimination of 5-FU rather than to a decrease in its renal excretion.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fluoruracila
/
Analgésicos Opioides
/
Fígado
/
Morfina
/
Antimetabólitos Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Estados Unidos