Table 3.

Mechanisms of elimination of antipsychotic drugs, their active metabolites and their effects on metabolism enzymes and P-gp.

Antipsychotic	The Main Route(s) of Elimination and Transporter Proteins Involved in the Distribution	Possible Mechanisms of Interactions
		Inducing or Inhibiting Effects on CYP, UGT and P-gp	Main Active Metabolite
Chlorpromazine	CYP2D6 P-gp	CYP2D6 inhibitor	7-Hydroxychlorpromazine
Trifluoperazine	CYP1A2	-	N-oxide trifluoperazine possibly active
Haloperidiol	CYP3A4 and CYP2D6 P-gp	CYP2D6 weak inhibitor P-gp substrate	Active metabolites not clinically relevant
Ziprasidone	CYP3A4 and aldehyde oxidase	CYP2D6 and CYP3A4 weak inhibitor	-
Lurasidone	CYP3A4	-	-
Paliperidone	Renal excretion CYP2D6 and CYP3A4 minimally involved	-	-
Pimozide	CYP3A4 and, to a minor extent, CYP1A2 and CYP2D6	P-gp substrate	-
Clozapine	CYP1A2 and, to a minor extent, CYP3A4 P-gp	-	-
Olanzapine	CYP1A2 and CYP2D6 and UGT P-gp	P-gp inhibitor	N-desmethyl and 2-hydroxymethyl metabolites (low clinical relevance)
Quetiapine	CYP3A4 P-gp	CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 weak inhibitor	Norquetiapine
Asenapine	CYP1A2 and, to a minor extent, CYP2D6 and CYP3A4, and UGT1A4	Weak CYP2D6 inhibitor	-
Sulpiride	Mainly cleared unchanged in urine	-	-
Risperidone	CYP2D6 and, to a lesser extent, CYP3A4 P-gp	P-gp inhibitor	9-Hydroxy-risperidone (paliperidone)
Aripiprazole	CYP3A4 and CYP2D6 P-gp	-	Dehydroaripiprazole
Paliperidone	Renal excretion and, to a minor extent, CYP2D6 and CYP3A4 P-gp	-	-
Iloperidone	CYP3A4 and CYP2D6	Weak CYP3A4 inhibitor	P88 and P95
Cariprazine	CYP3A4 and, to a minor extent, CYP2D6	P-gp inhibitor	Desmethyl cariprazine and didesmethyl cariprazine
Brexipiprazole	CYP3A4 and CYP2D6	-	-

Note: Antipsychotics are listed in the same order they appear in the ATC system. For a source of references, see Akamine et al. [17], O'Brien et al. [20], Spina et al., [22] and SmPC of each AP.

For abbreviations, see Table 2.