High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers

Chopra, Nitin; Ruan, Changgeng; McCollum, Betsy; Ognibene, Judy; Shelton, Charles; León, José de

doi:10.1016/j.rcpeng.2020.04.002

Cited by 1 publication

(3 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, biological diversity has not received enough attention in psychopharmacology practice, in general, and in patients of East Asian ancestry, specifically. Supplementary Table 14 (in the online-only Data Supplement) uses as examples four other psychiatric drugs (diazepam, 52,[180][181][182][183][184] carbamazepine, [185][186][187] olanzapine, 21,25,131,157,188 and haloperidol 24,61,64,[189][190][191] ) in which paying attention to East Asian ancestry may be important. The literature provides reasonable information concerning lower diazepam dosing in East Asians and for genotyping human leukocyte antigen-B*15:02 before starting carbamazepine in East Asian countries, except Japan.…”

Section: Further Reflections On Ethnopsychopharmacology Relevant For ...mentioning

confidence: 99%

“…• In typical doses, diazepam is mainly metabolized by CYP2C19 but at higher diazepam doses, the relative contribution of CYP3A4 ↑. 52 In CYP2C19 PMs it is metabolized by CYP3A4. 52 • CYP2C19 PMs are frequent in East Asia with an average prevalence of 13% (versus 2% in Europeans) 180 and they have twice the serum concentrations of normal metabolizers.…”

Section: Supplementary Table 1 the Need For An Open-minded Readermentioning

confidence: 99%

“…52 In CYP2C19 PMs it is metabolized by CYP3A4. 52 • CYP2C19 PMs are frequent in East Asia with an average prevalence of 13% (versus 2% in Europeans) 180 and they have twice the serum concentrations of normal metabolizers. 181 • As CYP2C19 PMs appear to have longer diazepam half-life and may have a higher risk of diazepam-induced sedation, 182 physicians from East Asian countries have empirically prescribed lower doses in East Asian populations than those recommended in the West.…”

Section: Supplementary Table 1 the Need For An Open-minded Readermentioning

confidence: 99%

See 2 more Smart Citations

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

León

2023

Psychiatry Investig

View full text Add to dashboard Cite

This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300-450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300-600 mg/day), assuming no poor metabolism (PM) status. Ancestry's impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.

show abstract

Section: Further Reflections On Ethnopsychopharmacology Relevant For ...mentioning

confidence: 99%

Section: Supplementary Table 1 the Need For An Open-minded Readermentioning

confidence: 99%

Section: Supplementary Table 1 the Need For An Open-minded Readermentioning

confidence: 99%

See 1 more Smart Citation

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

León

2023

Psychiatry Investig

View full text Add to dashboard Cite

show abstract

High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers

Cited by 1 publication

References 75 publications

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

Contact Info

Product

Resources

About