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- Lindnér, Per, 1956, et al.
(författare)
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Regional lymphatic drug exposure following intraperitoneal administration of 5-fluorouracil, carboplatin, and etoposide.
- 1993
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Ingår i: Surgical oncology. - 0960-7404. ; 2:2, s. 105-12
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Tidskriftsartikel (refereegranskat)abstract
- Intraperitoneal (i.p.) administration of chemoterapeutic agents results in greater total drug exposures in the peritoneal cavity than in plasma. A study on the drug exposure for i.p. lymphatics of pigs, receiving 5-fluorouracil (5-FU), etoposide (VP-16) and carboplatin (CBDCA) by the i.p. route was conducted. Drug concentrations in peritoneal fluid, plasma, and thoracic duct lymph were monitored over the ensuing 3 h. 5-FU appeared rapidly in thoracic duct, lymph and plasma. The lymph concentration declined after 20 min while the plasma concentration remained stable. CBDCA reached a stable concentration in lymph and plasma after 60 min. VP-16 peaked in the lymph after 20 min, whereas the plasma concentration continued to rise for 150 min; the peritoneal half-life for VP-16 was too long for clearance to be defined. Total drug exposure (AUC) was for 5-FU 5.7-fold greater for lymph than for plasma and for CBDCA equal in both compartments. VP-16 had a 2.1-fold higher AUC for lymph than for plasma. The results indicate that the i.p. route of administration results in a greater exposure of the lower thoracic duct lymph than the plasma to 5-FU, produces only a marginally increased exposure to VP-16, and results in no difference for CBDCA. The efficacy of 5-FU is a function of total drug exposure. The results reported provide a strong rationale for evaluating the adjuvant use of i.p. 5-FU in colorectal and gastric carcinoma.
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| 2. |
- Naredi, Peter, 1955, et al.
(författare)
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The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma.
- 1993
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 54:4, s. 645-9
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Tidskriftsartikel (refereegranskat)abstract
- The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha-treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro.
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