Maprotiline metabolism

PROPANOLOL MAPROTILINE Cases of T plasma levels of maprotiline with propanolol Uncertain at present. Postulated that maprotiline metabolism 1 by alterations in hepatic blood flow Monitor plasma levels of maprotiline when initiating beta-blocker therapy... 

Rotzinger, S, Bourin, M, Akimoto, Y, Coutts, RT and Baker, GB (1999) Metabolism of some second and fourth generation antidepressants iprindole, viloxazine, buproprion, mianserin, maprotiline, trazodone, nefazodone and venlafaxine. Cell. Molec. Neurobiol. 19 427 42. 

Amoxapine is also rapidly absorbed with protein binding of about 85%. The half-life is variable, and the drug is often given in divided doses. Amoxapine undergoes extensive hepatic metabolism. One of the active metabolites, 7-hydroxyamoxapine, is a potent D2 blocker and is associated with antipsychotic effects. Maprotiline is similarly well... 

In three patients, maprotiline plasma concentrations increased when risperidone was added (28). The rise was explained by inhibition of CYP2D6, by which maprotiline is mainly metabolized. 

Disposition in the Body. Slowly but completely absorbed following oral administration. It appears to undergo significant first-pass metabolism bioavailability about 70%. After intravenous administration, about 57% of a dose is excreted in the urine and 30% in the faeces over a period of 21 days less than 10% of the dose is excreted as unchanged drug. The principal metabolite is the desmethyl derivative, which has been shown to be active in animals, but hydroxylation also occurs to form phenolic derivatives which may be further converted to aromatic methoxy ethers or excreted as glucuronide conjugates A -oxidation also occurs and maprotiline A -oxide has been reported to be active numerous minor metabolites have been identified in urine. 

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. 

Gradual increases in maprotiline levels over 6 to 7 weeks during concurrent risperidone therapy have been found in 2 other patients. One of the patients was also taking nortriptyline, but its levels were unaltered. Maprotiline is mainly metabolised by the cytochrome P450 isoenzyme CYP2D6. The increased levels of maprotiline may be due to an inhibition of CYP2D6-mediated metabolism by risperidone. This interaction is... 

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