Dose and time dependencies of 5-fluorouracil pharmacokinetics

Terret, C.; Erdociain, Eric; Guimbaud, Rosine; Boisdron‐Celle, Michèle; McLeod, Howard L.; Féty‐Deporte, Régine; Lafont, Thierry; Gamelin, Érick; Bugat, R.; Canal, Pierre; Chatelut, Étienne

doi:10.1067/mcp.2000.109352

Cited by 54 publications

(52 citation statements)

References 23 publications

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“…The IC 50 values and their 95% confidence intervals are shown in Table 1. For DOX and 5FU, the doses selected are consistent with physiologic doses expected in patients receiving treatment with DOX (Gewirtz 1999) or 5FU (Peters et al 1993;Terret et al 2000). This experimental design was aimed at defining the steady-state transcriptional response of these cell lines to toxicants and on defining chemotherapeutic-specific responses that were consistent over time.…”

Section: Toxicant-specific Transcriptional Responsesmentioning

confidence: 99%

Prediction of Toxicant-Specific Gene Expression Signatures after Chemotherapeutic Treatment of Breast Cell Lines

Troester¹,

Hoadley²,

Parker³

et al. 2004

Environ Health Perspect

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Global gene expression profiling has demonstrated that the predominant cellular response to a range of toxicants is a general stress response. This stereotyped environmental stress response commonly includes repression of protein synthesis and cell-cycle-regulated genes and induction of DNA damage and oxidative stress-responsive genes. Our laboratory recently characterized the general stress response of breast cell lines derived from basal-like and luminal epithelium after treatment with doxorubicin (DOX) or 5-fluorouracil (5FU) and showed that each cell type has a distinct response. However, we expected that some of the expression changes induced by DOX and 5FU would be unique to each compound and might reflect the underlying mechanisms of action of these agents. Therefore, we employed supervised analyses (significance analysis of microarrays) to identify genes that showed differential expression between DOX-treated and 5FU-treated cell lines. We then used cross-validation analyses and identified genes that afforded high predictive accuracy in classifying samples into the two treatment classes. To test whether these gene lists had good predictive accuracy in an independent data set, we treated our panel of cell lines with etoposide, a compound mechanistically similar to DOX. We demonstrated that using expression patterns of 100 genes we were able to obtain 100% predictive accuracy in classifying the etoposide samples as being more similar in expression to DOX-treated than to 5FU-treated samples. These analyses also showed that toxicant-specific gene expression patterns, similar to general stress responses, vary according to cell type.

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Section: Toxicant-specific Transcriptional Responsesmentioning

confidence: 99%

Prediction of Toxicant-Specific Gene Expression Signatures after Chemotherapeutic Treatment of Breast Cell Lines

Troester¹,

Hoadley²,

Parker³

et al. 2004

Environ Health Perspect

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“…The population PK model of both 5-FU and 5-FDHU in colorectal cancer patients was based on a three compartment model with first order elimination process for 5-FU and 5-FDHU from the central compartment, and a saturated metabolism process of 5-FU towards 5-FDHU. The need to use a saturated metabolism model of Michaelis-Menten type was supported by previous modeling studies [16][17]. Since 5-FDHU was not administered alone, distribution volume of the metabolite was structurally non identifiable and was fixed to be equal to the distribution volume of 5-FU.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Analysis of 5-FU and 5-FDHU in Colorectal Cancer Patients: Search for Biomarkers Associated with Gastro-Intestinal Toxicity

Woloch¹,

Paolo²,

Marouani³

et al. 2012

CTMC

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“…In this study we used antineoplastic concentrations reached in patient treatment [26,27,28] or previously used in in vitro trials [6]. Some of these concentrations are similar to what has been shown in ‘momentary maximal concentration in the extracellular fluid’ [35].…”

Section: Discussionmentioning

confidence: 99%

“…Clinically achievable plasma levels were used, i.e. fluorouracil (50 µg/ml) [26], vincristine (0.5 µg/ml) [27] and doxorubicin (15 µg/ml) [28]. Concentrations previously used in vitro were chosen for the other agents, i.e.…”

Section: Methodsmentioning

confidence: 99%

Unchanged Antibiotic Susceptibility in <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> after Long-Term in vitro Exposure to Antineoplastic Drugs

et al. 2012

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Background: Certain antineoplastic drugs inhibit bacterial growth. Whether these drugs also cause genetic changes in bacteria that lead to increased antibiotic resistance is not yet documented. Given the massive and repeated antibiotic treatment most cancer patients undergo, this question is important. We have examined the possible effects of in vitro long-term antineoplastic exposure on antibiotic resistance. Methods: Using the disc diffusion method, two bacterial strains (Escherichia coli, ATCC 25922, and Pseudomonas aeruginosa, ATCC 27583) were exposed to methotrexate, fluorouracil, vincristine, doxorubicin and cytarabine during 50 overnight cycles. The bacterial strains were susceptibility-tested to several antibiotics before and after repeated exposure to antineoplastics. Results: No changes in antibiotic susceptibility were seen in the two bacterial strains after long-term exposure to any of the antineoplastic drugs tested. Conclusion: Long-term in vitro antineoplastic exposure did not change the antibiotic susceptibility in the E. coli or P. aeruginosa strains.

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Dose and time dependencies of 5-fluorouracil pharmacokinetics

Abstract: The pharmacokinetic parameters obtained in this study would be useful to predict the 5-fluorouracil plasma concentrations following other schedules of administration of 5-fluorouracil and to study the possible pharmacokinetic interactions between 5-fluorouracil and other drugs.

Cited by 54 publications

References 23 publications

Prediction of Toxicant-Specific Gene Expression Signatures after Chemotherapeutic Treatment of Breast Cell Lines

Prediction of Toxicant-Specific Gene Expression Signatures after Chemotherapeutic Treatment of Breast Cell Lines

Population Pharmacokinetic Analysis of 5-FU and 5-FDHU in Colorectal Cancer Patients: Search for Biomarkers Associated with Gastro-Intestinal Toxicity

Unchanged Antibiotic Susceptibility in <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> after Long-Term in vitro Exposure to Antineoplastic Drugs

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