The physiologic disposition of 5‐fluorouracil and 5‐fluoro‐2′‐deoxyuridine in man

Clarkson, Bayard D.; O'Connor, Annabel; Winston, LaReine; Hutchison, Dorris J.

doi:10.1002/cpt196455581

Cited by 132 publications

(21 citation statements)

References 16 publications

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“…In man there are more degradation products in the general circulation and expired air and less urinary excretion of unchanged 5-FU recorded after oral as compared to intravenous administration [5,10]. These findings combined with our experiences in pigs strongly indicate that 5-FU is degraded in the liver and that this makes the ground for the ra tionale of regional administration of 5-FU to patients with cancer in that organ.…”

Section: Discussionsupporting

confidence: 62%

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Inactivation of 5-Fluorouracil by the Liver during Continuous Regional and Systemic Infusion in Pigs

Almersjö¹,

Brandberg²,

Gustavsson³

et al. 1976

Eur Surg Res

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During continuous systemic or portal infusion of 5-fluorouracil (5-FU) to anaesthetized pigs, the cytostatic activity was reduced in blood traversing the liver. The liver eliminated between 15 and 5G% of the amount 5-FU given per time unit. During jugular infusion the concentration of cytostatic compounds in portal blood was equal to or less than in systemic blood. The cytostatic activity was much higher in portal blood and lower in systemic blood during portal infusion. The findings speak in favour of portal infusions of 5-FU to patients with disseminated cancer in the liver.

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Section: Discussionsupporting

confidence: 62%

“…Bile was continuously collected. The concentration of 5-FU in the samples was mea sured by the microbiologic agar plate technique [5]. 14-cm agar plates were inocu lated with Streptococcus faecalis (ATCC 8043) cultured in a uracil-free medium.…”

Section: Methodsmentioning

confidence: 99%

Inactivation of 5-Fluorouracil by the Liver during Continuous Regional and Systemic Infusion in Pigs

Almersjö¹,

Brandberg²,

Gustavsson³

et al. 1976

Eur Surg Res

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“…Some data are available on the plasma concentrations of FU after i.v. injection or oral administration (Cohen et al, 1974), but only one other published study (Clarkson et al, 1964) besides our preliminary report gives data on plasma concentrations of drug during continuous i.v. infusion.…”

mentioning

confidence: 68%

Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion

Hillcoat¹,

McCulloch²,

Figueredo³

et al. 1978

Br J Cancer

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Summary.-Concentrations of 5-fluorouracil (FU) were measured in the plasma of patients receiving i.v. infusions of the drug for 5 days as treatment for adenocarcinoma of the gastrointestinal tract. Concentrations of FU varied widely in many patients. Concentration of drug x time of infusion (C x t values) were calculated.Patients showing a partial response or stabilization of disease had significantly higher C x t values than non-responders. Methyl CCNU did not affect the C x t values of FU. Determination of the plasma concentration of FU would allow the dose of the drug to be adjusted to maintain high concentrations of FU in the plasma. Our data suggest that such high concentrations would increase the response rate in this disease.

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“…The method was essentially the same as that described by Clarkson et al 22 The strain Streptococcusfaecium var. durans (SF/O) was maintained as described by H~t c h i s o n~~ on the folic acid medium of Flynn et a1.…”

Section: Microbiological Assaymentioning

confidence: 99%

Comparison of gas chromatographic/mass spectrometric and microbiological assays for 5-fluorouracil in plasma

Min

Garland

Lewinson

et al. 1985

Biol. Mass Spectrom.

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The concentrations of 5-fluorouracil in 99 plasma samples were determined by both microbiological and gas chromatographic/mass spectrometric assays. The values determined by the two methods were similar (correlation coefficient = 0.90). A regression of the natural logarithms of the concentrations (0.01-94 micrograms ml-1) determined by the two methods gave a line whose slope and intercept were not statistically different (p greater than 0.05) from 1 and 0 respectively. Thus, the microbiological assay has specificity over a sufficient concentration range to serve as a practical routine laboratory method for the determination of 5-fluorouracil.

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The physiologic disposition of 5‐fluorouracil and 5‐fluoro‐2′‐deoxyuridine in man

Abstract: The plasma concentration and the urinary excretion of and Since the synthesis of 5-Huorouracil (FU) and the demonstration of its biologic activity were reported in 1957,24, 33 a

Cited by 132 publications

References 16 publications

Inactivation of 5-Fluorouracil by the Liver during Continuous Regional and Systemic Infusion in Pigs

Inactivation of 5-Fluorouracil by the Liver during Continuous Regional and Systemic Infusion in Pigs

Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion

Comparison of gas chromatographic/mass spectrometric and microbiological assays for 5-fluorouracil in plasma

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