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Metabolism of
antipsychotic drugs usually starts with oxidation by hepatic microsomal enzymes (P450
system), followed by glucuronidation and excretion in urine. After long-term use, the rate
of conversion of parent drug increases slightly, causing a mild metabolic tolerance;
however, monitoring the blood concentration of drug is generally not useful in preventing
this problem. In individual patients, very wide variations in blood concentration of
antipsychotic agent can still achieve control of symptoms. Thioridazine because of its
prominent anticholinergic activity in the gastrointestinal tract, may display erratic
absorption after oral administration. Even with regular dosing, especially in older
patients, periods of inadequate or excessive blood concentrations of drug may result. |