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Monoketocholate can decrease transcellular permeation of methotrexate across Caco-2 cell monolayers and reduce its

Gong Chen¹, J Paul Fawcett, Momir Mikov

¹School of Pharmacy, University of Otago, Dunedin, New Zealand.

The Journal of Pharmacy and Pharmacology

|July 11, 2009

Summary

This summary is machine-generated.

Bile salts like sodium 12-monoketocholate can reduce methotrexate absorption in rats. This occurs by inhibiting transcellular active transport, impacting drug bioavailability.

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Area of Science:

Pharmacology and Toxicology
Gastrointestinal Physiology

Background:

Bile salts are known to affect drug absorption through unknown mechanisms.
Methotrexate absorption in the rat intestine is decreased by bile salts.

Purpose of the Study:

To investigate the mechanism by which bile salts influence methotrexate intestinal absorption.
To evaluate the in vitro-in vivo correlation of bile salt effects on methotrexate absorption.

Main Methods:

Assessed apical-to-basolateral (AP-BL) permeation of methotrexate across Caco-2 cell monolayers pretreated with varying concentrations of sodium cholate or sodium 12-monoketocholate.
Determined the effect of orally administered sodium 12-monoketocholate on methotrexate intestinal absorption in rats.

Main Results:

Sodium cholate and sodium 12-monoketocholate altered methotrexate AP-BL permeation in a concentration-dependent manner, with inhibition at lower concentrations and enhancement at higher concentrations.
Higher bile salt concentrations disrupted Caco-2 cell monolayer integrity, while lower concentrations did not.
Oral administration of sodium 12-monoketocholate at 40 and 80 mg/kg significantly reduced methotrexate absorption in rats.

Conclusions:

Sodium 12-monoketocholate decreases intestinal absorption of methotrexate in rats.
The mechanism involves the inhibition of transcellular active transport of methotrexate.