Pharmacokinetic Interaction between Nortriptyline and Terbinafine
P.H.M. van der Kuy, Harrie A van den Heuvel, Rob W Kempen, Leo M L Vanmolkot
Abstract
P.H.M. van der Kuy, Harrie A van den Heuvel, Rob W Kempen, Leo M L Vanmolkot
Abstract
OBJECTIVE: To clarify the mechanism of interaction between nortriptyline and terbinafine. CASE SUMMARY: Nortriptyline intoxication secondary to terbinafine treatment was observed in a woman with a major depressive disorder. This is the second report of this interaction. A rechallenge was performed during which serum concentrations were measured of nortriptyline and the 2 hydroxy metabolites. To document the case, genotyping of CYP2D6 was also performed. DISCUSSION: Metabolism by CYP2D6 is of major importance for the hydroxylation of nortriptyline, making it susceptible to competitive inhibition by terbinafine. CONCLUSIONS: The pharmacokinetic interaction between nortriptyline and terbinafine is probably due to inhibition of CYP2D6 of the nortriptyline metabolism by terbinafine. The interaction is not restricted to a subpopulation, but may occur even in persons without deviations in CYP2D6.
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OBJECTIVE: To clarify the mechanism of interaction between nortriptyline and terbinafine. CASE SUMMARY: Nortriptyline intoxication secondary to terbinafine treatment was observed in a woman with a major depressive disorder. This is the second report of this interaction. A rechallenge was performed during which serum concentrations were measured of nortriptyline and the 2 hydroxy metabolites. To document the case, genotyping of CYP2D6 was also performed. DISCUSSION: Metabolism by CYP2D6 is of major importance for the hydroxylation of nortriptyline, making it susceptible to competitive inhibition by terbinafine. CONCLUSIONS: The pharmacokinetic interaction between nortriptyline and terbinafine is probably due to inhibition of CYP2D6 of the nortriptyline metabolism by terbinafine. The interaction is not restricted to a subpopulation, but may occur even in persons without deviations in CYP2D6.
Key concepts: Nortriptyline, Terbinafine, CYP2D6, Pharmacology, Pharmacokinetics, Medicine, Drug interaction, Internal medicine