Changes in toxic and antitumor properties of ftorafur by induction or inhibition of the microsomal enzymes activity

Belitsky, Gennady A.; Бухман, В. М.; Konopleva, I. A.

doi:10.1007/bf00262340

Cited by 3 publications

(2 citation statements)

References 3 publications

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“…However, these data are not confirmed by experimental studies which demonstrated cross-resistance of TG and 5-FU in mice bearing L1210 lymphocytic leukaemia (Garibjarian et al, 1976). Initial pharmacological studies showed that TG is a pro-drug of 5-FU for it is slowly metabolised in the liver by microsomal enzymes to 5-FU (Belitsky et al, 1981). 5-FU is in turn slowly released into the systemic circulation where it reaches detectable levels for a prolonged period of time (Garibjanian et al, 1976;Benvenuto et al, 1978;Schilcher et al, 1983).…”

Section: Italymentioning

confidence: 99%

Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study

Palmeri

Gebbia²,

Russo³

et al. 1990

Br J Cancer

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Section: Italymentioning

confidence: 99%

Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study

Palmeri

Gebbia²,

Russo³

et al. 1990

Br J Cancer

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“…Many efforts have been made to increase the antitumor activity of FT by obtaining a high plasma concen tration of 5-FU (6,7). In the previous paper (8), we reported that the plasma concen trations of both FT and 5-FU increased after administration of FT (500 mg/kg, p.o.)…”

Section: (Tetrahydro 2 Furanyl) 5 Fluorouracil (Ft)mentioning

confidence: 99%

Effect of L-Cysteine on Distribution Volume of 1-(Tetrahydro-2-Furanyl)-5-Fluorouracil

Kawabata¹,

Yano²,

Ohno³

et al. 1990

Japanese Journal of Pharmacology

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Abstract-Higher plasma concentrations of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) were obtained after administration of FT (100 mg/kg, i.v.) combined with L cysteine (CySH, 500 mg/kg, p.o.). The volume of distribution (Vd) and body fluid volumes significantly decreased.These results suggest that the increase of the plasma concentrations of FT can be attributed to the decrease of the Vd of FT, which is considered to be based on the decrease of body fluid volumes by the combined administration of CySH. 1 (Tetrahydro 2 furanyl) 5 fluorouracil (FT) is considered a prodrug of 5-fluorouracil (5-FU) and exerts antitumor activity through metabolic activation (1-5). Many efforts have been made to increase the antitumor activity of FT by obtaining a high plasma concen tration of 5-FU (6, 7). In the previous paper (8), we reported that the plasma concen trations of both FT and 5-FU increased after administration of FT (500 mg/kg, p.o.) combined with L-cysteine (CySH, 500 mg/ kg, i.p. or p.o.) when compared to FT alone.The purpose of this study was to elucidate the mechanism of the CySH effect in the previously reported results (8). We tried to examine the effect of CySH on FT distribution in terms of the pharmacokinetic aspects. Body fluid volumes were also measured to investigate its relationship with FT distribution after oral administration of FT alone or combined with CySH.Male Wistar rats (150-178 g) were fasted overnight before drug administration and during the experiment, and they were given water ad libitum. Rats were given FT (100 mg/kg, i.v.; Aldrich) alone or combined with CySH (500 mg/kg, p.o.; Nippon Rikagaku yakuhin, Co.) at 1 and 4 hr before and at 2 hr after administration of FT. Rats were lightly anesthetized with diethyl ether, and blood was drawn into heparinized tubes by the interorbital sinus bleeding technique at definite times after drug administration. After centrifugation at 2,500 r.p.m. for 10 min, the resulting plasma was collected.In a separate experiment, other groups of rats were given FT (500 mg/kg, p.o.) alone or combined with CySH (500 mg/kg, p.o.). Urine was sampled up to 4 hr after drug administration, and the volume was measured.FT was extracted from plasma according to the method of Wu et al. (9). After ex traction, ethyl acetate was evaporated to dryness under vacuum at room temp. The residue was dissolved in 100 acl of methanol, and a 5-id aliquot was injected into a Hitachi Model 635 high performance liquid chromatograph with a JASCO Model UVIDEC-100-V absorbance detector at 280 nm. The mobile phase was 15% methanol in 0.01 M acetate buffer (pH 4.2) at a flow rate of 1 ml/min. The precolumn (50x4.6 mm i.d.) and the analytical column (250x4.6 mm i.d.) were reverse phase columns (5 am, octadecyl, Gasukuro Kogyo Inc., Tokyo) and were maintained at a temp. of 50°C.Body fluid volumes in rats 4 hr after administration of FT (500 mg/kg, p.o.) alone or combined with CySH (500 mg/kg, p.o.) were determined according to the method of Bianchi et al. (10).The hematocrit value was measured af...

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Clinical Studies of the Modulation of Ftorafur

Creaven¹,

Rustum²,

Petrelli³

et al. 1993

Advances in Experimental Medicine and Biology

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Changes in toxic and antitumor properties of ftorafur by induction or inhibition of the microsomal enzymes activity

Cited by 3 publications

References 3 publications

Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study

Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study

Effect of L-Cysteine on Distribution Volume of 1-(Tetrahydro-2-Furanyl)-5-Fluorouracil

Clinical Studies of the Modulation of Ftorafur

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