The effect of repeated oral dosing of methotrexate on its intestinal absorption in the rat

Jolly, Lewis E.; Fletcher, H. Patrick

doi:10.1016/0041-008x(77)90173-9

Cited by 25 publications

(13 citation statements)

References 8 publications

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“…On the other hand, orally dosed MTX enhances the intestinal absorption of MTX itself (22). Following daily oral dosing of 0.07 mg/kg/day MTX to rats for 8 days, the infiltration of inflammatory cells and the blunting of villi are observed (22). Following daily oral dosing of 0.6 mg/kg/day MTX to rats for 6 days, extensive mucosal damages with marked inflammatory cell infiltration and denuded villi are observed (22).…”

Section: Introductionmentioning

confidence: 99%

“…It also decreases the intestinal absorption (19,20), metabolic activities and active transport capacities (18,21) of some drugs. On the other hand, orally dosed MTX enhances the intestinal absorption of MTX itself (22). Following daily oral dosing of 0.07 mg/kg/day MTX to rats for 8 days, the infiltration of inflammatory cells and the blunting of villi are observed (22).…”

Section: Introductionmentioning

confidence: 99%

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Variability of oral bioavailability for low dose methotrexate in rats

Kuroda¹,

Namba²,

Torimaru³

et al. 2001

Eur. J. Drug Metab. Pharmacokinet.

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The effects of food, antibiotics, diclofenac sodium (DS) and methotrexate (MTX) on oral bioavailability (BA) of MTX were examined in rats. Feeding didn't vary the plasma concentrations after intravenous dosing of 0.5 mg/kg MTX, but enhanced those after oral dosing, and the oral BA. The twice daily oral doses of 40 mg/kg neomycin sulfate (NS) or mixed antibiotics (200 mg/kg NS + 200 mg/kg streptomycin sulfate + 200 mg/kg bacitracin) for 5 days didn't influence the plasma concentrations after intravenous dosing of 0.5 mg/kg MTX, but induced the decreased Cmax and the delayed MRT after oral dosing. The plasma concentrations after intravenous or oral dosing of 2.5 mg/kg MTX in rats orally dosed with 1 or 5 mg/kg/day DS for 4 days were similar to those in the control rats, while the pre-treatment of 25 mg/kg/day DS delayed the elimination of MTX but didn't change the oral BA. The plasma concentrations after intravenous or oral dosing of 2.5 mg/kg MTX in rats, which received the intermittent oral doses of 7.5 mg/kg/3 doses/week MTX for 4 weeks, were comparable to those in the control rats, but the daily pre-treatment of 0.2 mg/kg/day MTX for 4 weeks increased the plasma concentrations after oral dosing, and the BA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variability of oral bioavailability for low dose methotrexate in rats

Kuroda¹,

Namba²,

Torimaru³

et al. 2001

Eur. J. Drug Metab. Pharmacokinet.

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“…(Shaw et al, 1979). MTX in particular has been shown to cause villus atrophy in the experimental animal with malabsorption of a wide (Jolly & Fletcher, 1977;Vehno, 1976). In children with acute leukaemia malabsorption syndromes may not* be associated with such severe structural dysruption and the precise cause of the functional abnormalities is less clear.…”

mentioning

confidence: 99%

“…It is possible that repeated inhibition of crypt cell division over several weeks leads to a similar imbalance in villus cell turnover. The relative sparing of structure and function after biweekly low dose MTX by comparison with low daily or alternative day doses (Jolly & Fletcher, 1977;Baskerville & Batter-Hatten, 1977) could have been due either to the lower cumulative dose or to the greater time interval between doses. If insufficient time is allowed between doses the failure of mitotic recovery leads to crypt hypoplasia and villus atrophy.…”

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confidence: 99%

Methotrexate enterotoxicity: Influence of drug dose and timing in the rat

Pinkerton¹,

Milla²

1984

Br J Cancer

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“…Since garlic extracts have been shown to protect organs from various injuries (Horie et al, 1992;Nakagawa et al, 1989), the protective effect of the aqueous garlic extract on MTX-induced damage to intestinal mucosa was investigated. It has long been known that MTX causes severe damage to the intestinal mucosa (Robinson et al, 1966;Jolly and Fletcher, 1977). This model of intestinal mucositis is characterized histologically by crypt loss, villus fusion and atrophy, gross capillary dilatation, a mixed cellular infiltrate and a rapid recovery (Taminiau et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Effect of aged garlic extract against methotrexate‐induced damage to the small intestine in rats

Yüncü

Eralp

Çelik

2006

Phytotherapy Research

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Methotrexate (MTX) chemotherapy is often accompanied by side effects such as gastrointestinal ulceration and diarrhea. The aim of this study was to examine histologically whether an aged garlic extract (AGE) had a protective effect on the small intestine of rats with MTX-induced damage. Forty male Wistar albino rats were randomized into experimental and control groups and divided into four groups of ten animals. To the first group, MTX was applied as a single dose (20 mg/kg) intraperitoneally. To the second group, in addition to MTX application, AGE (250 mg/kg) was administered orally every day at the same time by intragastric intubation until the rats were killed. To the third group, AGE only was given. The fourth group was the control. All animals were killed 4 days after the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA levels. Before killing, intracardiac blood was obtained from each animal to perform biochemical analysis (plasma lactate level). MTX was found to lead to damage in the jejunal tissues and to increase the MDA and lactate levels in the plasma. Administration of the AGE decreased the severity of jejunal damage, but increased MDA and lactate levels caused by MTX treatment on the other hand. These results suggest that AGE may protect the small intestine of rats from MTX-induced damage. Thus this study substantiated the thought that the protective effect of AGE is derived from the manner in which it interacts with crypt cells.

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The effect of repeated oral dosing of methotrexate on its intestinal absorption in the rat

Cited by 25 publications

References 8 publications

Variability of oral bioavailability for low dose methotrexate in rats

Variability of oral bioavailability for low dose methotrexate in rats

Methotrexate enterotoxicity: Influence of drug dose and timing in the rat

Effect of aged garlic extract against methotrexate‐induced damage to the small intestine in rats

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