Table 1.
Summary of drug-specific pharmacokinetic properties, side-effects and overdosing risks in women
| Pharmacokinetics | Risk for side-effects | Risk of overmedicating women as compared to men | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Metabolism1 | CYP-activity in females as compared to males2,3,4,5,6 | P-gp binding7,8,9 | QTc prolongation | Prolactin elevation | EPS and akathisia10 | Metabolic dysfunction | |||
| Weight gain10 | Lipid/glucose abnormalities12 | ||||||||
| Amisulpride | >90% renal excretion | ++/+++ | +++10 | +++10,12 | +10 | + | ++12 | ++ | |
| Aripiprazole | CYP2D6, CYP3A4 | (+), (+ +) | ++ | −10 | −10,12 | −/+10 | +10 | −12 | + |
| Chlorpromazine | CYP1A2a, CYP2D6 | (− −), (+) | + | ++11ψ | +10ψ | ++10ψ | +++10 | +++12ψ | ++ |
| Clozapine | CYP1A2a, CYP2C19a, CYP3A4 | (− −), (−), (++) | + | ++11ψ | −10,12 | −10 | +++10 | +++13 | +++ |
| Flupentixol | CYP2D6a | (+) | ? | +11ψ | −10 | +++10 | ++10 | ? | + |
| Haloperidol | CYP2D6a, CYP3A4 | (+), (+ +) | + | +10ψ | ++10.12 | +++10 | +10 | −13 | + |
| Lurasidone | CYP3A4 | (+ +) | ? | −10 | +/++10,12 | ++10 | +10 | −13 | +/− |
| Olanzapine | CYP1A2a | (− −) | ++/+++ | ++10 | +10,12 | −10 | +++10 | +++13 | +++ |
| Paliperidone | CYP3A4, UGT1A1, 60% renal excretion |
(++), (+) | ++/+++ | +10 | +++10.12 | +10 | +10 | ++13 | ++ |
| Quetiapine | CYP3A4, CYP2D6a | (++), (+) | −/+ | ++10 | −10.12 | −10 | +++10 | ++13 | − |
| Risperidone | CYP2D6a, CYP3A4 | (+), (++) | +++* | ++10 | +++10.12 | ++10 | ++10 | +13 | ++ |
| Sulpiride | Renal excretion only | ++/+++ | ++ | +++12ψ | ++10ψ | ++10 | ? | ++ | |
| Zuclopenthixol | CYP2D6 | (+) | ? | ? | ? | +++10 | +10 | ? | + |
CYP, cytochrome P450; EPS, extrapyramidal symptoms; P-gp, P-glycoprotein; UGT, UDP glucuronosyl transferase.
The risk of overmedicating women as compared to men is estimated based on drug-specific metabolism, P-gp binding and CYP-activity in women compared to men. In addition, the risk of QTc prolongation, prolactin elevation, EPS and akathisia, weight gain and lipid/glucose abnormalities are also defined.
1, Hiemke et al. (2018); 2, Scandlyn et al. (2008); 3, Choi et al. (2013); 4, Piccinato et al. (2017); 5, Hagg et al. (2001); 6, Tamminga et al. (1999); 7, Doran et al. (2005); 8, Linnet & Ejsing (2008); 9, Nagasaka et al. (2012); 10, Huhn et al. (2019); 11, Wenzel-Seifert et al. (2011); 12, Peuskens et al. (2014); 13, De Hert et al. (2012).
(++), activity strongly higher in females; (+), activity higher in females; only of relevance during pregnancy; (−), activity lower in females; (− −), activity strongly lower in females; a, inhibited by oral oestrogenic contraceptives; +++, high incidence/high severity/strong; ++, moderate incidence/moderate severity/moderate; +, light incidence/mild severity/mild; −, low/very low/small; ?, unknown; *, main metabolite of risperidone 9-OH-risperidone. ψ, level of evidence is limited. When enzymes are indicated in bold, drug plasma concentrations will significantly increase or decrease when combined with strong to moderate inducers or inhibitors (see Hiemke et al., 2018).