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Methotrexate may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE.
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Methotrexate may rarely be habit forming. Methotrexate should be avoided in patients with a history.
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This indicates that Methotrexate slightly decreases the precision of thermoregulatory control in addition to reducing the setpoint.

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The mean absolute bioavailability of a 100 mg oral dose is approximately 75%. The mean peak plasma concentration of racemic Methotrexate and M1 occurs at two and three hours, respectively, after administration in healthy adults.
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In general, both enantiomers of Methotrexate and M1 follow a parallel time course in the body following single and multiple doses although small differences (~10%) exist in the absolute amount of each enantiomer present.
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