Pharmacokinetic interaction between nortriptyline and terbinafine.
OBJECTIVE
To clarify the mechanism of interaction between nortriptyline and terbinafine.


METHODS
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.


CONCLUSIONS
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.
Van Der Kuy
P-Hugo M
PH
Department of Clinical Pharmacy and Toxicology, Academic Hospital Maastricht, Netherlands. hkuy@kfls.azm.nl
Van Den Heuvel
Harrie A
HA
Kempen
Rob W
RW
Vanmolkot
Leo M L
LM
D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000502:physiology; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009281:Naphthalenes / Q000493:pharmacokinetics*; D009661:Nortriptyline / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000077291:Terbinafine
D000929:Antidepressive Agents, Tricyclic; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009661:Nortriptyline; D019389:Cytochrome P-450 CYP2D6; D000077291:Terbinafine