Abstract | PURPOSE: METHODS: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. RESULTS: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P < 0.05) than in healthy lung tissue and showed pronounced interindividual variability. Median concentrations were 36.8 microg/g (26.9 44.2 microg/g) in healthy tissue and 5.1 microg/g (0.0-26.8 microg/g) in tumor samples. Tumor cyclophosphamide concentrations varied between 0 and 75% of those reached in healthy tissue. CONCLUSIONS: Our results indicate that CP tumor concentrations are modulated by factors different from dose and that expression of bioactivating enzymes in human lung or transfection of genes encoding these enzymes into tumor cells does not necessarily lead to local bioactivation of cyclophosphamide.
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Authors | F Bohnenstengel, G Friedel, C A Ritter, M McClellan, P Fritz, M Eichelbaum, A Linder, H Toomes, R Dierkesmann, H K Kroemer |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 45
Issue 1
Pg. 63-8
( 2000)
ISSN: 0344-5704 [Print] Germany |
PMID | 10647504
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Cyclophosphamide
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Topics |
- Aged
- Antineoplastic Agents, Alkylating
(pharmacokinetics)
- Biotransformation
- Carcinoma, Bronchogenic
(metabolism)
- Cyclophosphamide
(pharmacokinetics)
- Female
- Humans
- Lung
(metabolism)
- Lung Neoplasms
(metabolism)
- Male
- Middle Aged
- Perfusion
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