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

Jose de Leon(Jose de Leon ) 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.3

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.

El Tratado de Libre Comercio en América del Norte y el Crecimiento Económico en las Manufacturas Mexicanas

Adrian de Leon Arias 한국라틴아메리카학회 2007 라틴아메리카연구 Vol.20 No.3

Regional economic growth in Mexican manufacturing after trade liberalization in 1984-1985, and in particular under the North American Free Trade Agreement (NAFTA), signed in 1994, has been characterized by a faster growth in employment and output in the Northern Border region. In this article, these regional dynamics are analyzed and related to productivity, that is output per worker growth, in that region and compared to others regions in the country from 1970 to 2004. This study concludes that there is not a clear association between TLCAN and greater economic growth in the Northern Border region.

Dr. Pablo Mendes de Leon Director, International Institute of Air and Space Law Leiden University, Leiden, The Netherlands

Pablo Mendes de Leon 숭실대학교 법학연구소 1998 法學論叢 Vol.11 No.-

LIFTS OF DERIVATIONS TO THE TANGENT BUNDLE OF P^r-VELOCITIES

DE LEON, MANUEL,SALGADO, MODESTO Korean Mathematical Society 1986 대한수학회지 Vol.23 No.2

Socrates in the 21st century-A Justification of Skeptical Interventions in Narrative Encounters -

( Leon De Haas ) 한국철학상담치료학회 2018 철학 실천과 상담 Vol.8 No.-

In this essay, which is a summary of the main ideas in the author’s Ph.D. research (still work in progress), the author proposes a method to justify philosophical practice philosophically. Such a justification is necessary for the sake of the connection with academic philosophy and to avoid philosophical bungling. The author connects to Socrates’ skeptical and maieutic legacy, as well as to Husserl’s perceptive/experiential and Wittgenstein’s descriptive and ordinary language legacies. He explains his hypothesis that a philosopher might be aware of his epistemic premises and able to test these premises in the practice of philosophizing. He discusses his methodic and epistemic hypotheses, the latter being experiential and semantic questioning.

REGULAR P-ALMOST COTANGENT STRUCTURES

LEON, MANUEL DE,MENDEZ, ISABEL,SALGADO, MODESTO Korean Mathematical Society 1988 대한수학회지 Vol.25 No.2

유럽의 입장에서 본 국제민간항공분야의 전망

Leon, Pablo Mendes de 한국항공우주법학회 1994 한국항공우주정책·법학회지 Vol.6 No.-

Situational Philosophy : Towards a theory of philosophical practice

( Leon De Haas ) 한국철학상담치료학회 2012 철학 실천과 상담 Vol.3 No.-

This essay is a revised and expanded version of the text which was the basis for the author’s Masterclass at the 11th International Conference on Philosophical Practice (ICPP), the 18th of July 2012 at the Humanities Institute, Kangwon National University in Chuncheon, Republic of Korea. The main goal of the essay is, to contribute to a theory of philosophical practice. To do this, the author develops a criticism of reductionist practices in philosophy. The theoretical point of departure is an abridged survey of the two paradigmatic changes in European philosophy in the 20th century, i.e., Husserl’s phenomenology, and Wittgenstein’s language game analysis. The line of thinking is illustrated by a case story of the author. Part I discusses the phenomenological and linguistic turns in European philosophy. Part II describes and discusses a case story. Part III criticizes two forms of reductionism in philosophical practice, namely psychological and conceptual reductionism. Part IV gives an initial impetus to a theory of philosophical practice beyond any reductionism. In the present essay, the author is dealing with Western philosophy only, as the origins of post-Modern philosophical practice are rooted in Western philosophy. Lately, Eastern philosophy has been an inspiration for philosophical practice as well.

A Skeptic’s Look on Philosophical Therapy

Leon de Haas 강원대학교 인문과학연구소 2015 Journal of Humanities Therapy Vol.6 No.1

Philosophical practice is a historical and social phenomenon. As such it reflects and reproduces developments in the society which it is part of. In Western countries the post-industrial mass culture of the Self can be seen as a struggle with ‘nihilism’. Attempts to proclaim a philosophical therapy are both part of the culture of the Self, and, particularly, a sign of resistance against the loss of philosophical identity. In the context of the Industrial Revolution philosophy lost substantial crafts to the new sciences and humanities. In different ways, Husserl and Wittgenstein gave due consideration to that loss, and developed new practices of philosophy. Their paradigmatic innovations are known as the linguistic and phenomenological turns, the latter radicalized by Levinas. In this essay, the work of the three protagonists is called the ‘Open Senses’ paradigm. After World War II this paradigmatic revolution has been ignored, or at least debunked. Peter Raabe’s book on philosophical therapy is discussed as a present-day example of restorative philosophy in the field of philosophical practice.

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

de Leon Jose 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.4

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.