Maprotiline liver

As noted previously (SEDA-10, 21), hepatotoxicity has been described with maprotiline, and two further reports have been published. In one of these, hepatotoxicity was observed in a 54-year-old man treated with maprotiline for chronic head and neck pain (19). The other report described a patient who developed a marked increase in liver enzymes and symptoms during therapy with maprotiline and opipramol after withdrawal the patient recovered completely (20). 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

Maprotiline is slowly but completely absorbed from the Gl tract, and like the other TCAs, it is metabolized by the polymorphic CYP2D6 and CYP2C19 isoforms in the liver, primarily to pharmacologically active N-desmethylmaprotiline and to maprotiline-N-oxide. Its pharmacokinetics are shown in Table 21.3. Maprotiline is distributed into breast milk at concentrations similar to those found at steady state in maternal blood. The elimination half-life of maprotiline averages 43 hours (60-90 hours for its N-desmethyl metabolite). 

Not understood. A suggested reason is that the propranolol reduces the blood flow to the liver so that the metabolism of the maprotiline is reduced, leading to its accumulation in the body. 

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