Your browser doesn't support javascript.
loading
High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers / Dos pacientes que tomaban inductores necesitaron dosis altas de medicamentos metabolizados en gran medida por el CYP3A4 para alcanzar concentraciones terapéuticas
Chopra, Nitin; Ruan, Can-Jun; McCollum, Betsy; Ognibene, Judy; Shelton, Charles; de Leon, Jose.
  • Chopra, Nitin; Centre for Addiction and Mental Health. Addictions Division. Toronto. CA
  • Ruan, Can-Jun; Capital Medical University. Beijing Anding Hospital. Beijing Key Lab of Mental Disorders. Beijing. CN
  • McCollum, Betsy; Eastern State Hospital. Lexington. US
  • Ognibene, Judy; Eastside Psychiatric Hospital. Apalachee, Inc. Tallahassee. US
  • Shelton, Charles; Eastern State Hospital. Lexington. US
  • de Leon, Jose; Eastern State Hospital. University of Kentucky Mental Health Research Center. Lexington. US
Rev. colomb. psiquiatr ; 49(2): 84-95, abr.-jun. 2020. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1115648
ABSTRACT
ABSTRACT

Introduction:

In the last 20 years of clinical practice, the senior author has identified these 2 rare cases in which the patients needed extremely high doses of drugs metabolized by CYP3A4 to reach and maintain serum therapeutic concentrations.

Methods:

The high metabolic ability of these 2 patients was demonstrated by the low concentration-to-dose ratios (C/D ratios) of several drugs metabolized by CYP3A4.

Results:

Case 1 was characterized by a history of high carbamazepine doses (up to 2,000 mg/day) and needed 170 mg/day of diazepam in 2 days to cooperate with dental cleaning. The high activity of the CYP3A4 isoenzyme was manifested by fast metabolism for quetiapine and diazepam, which took more than 1 year to normalize after the inducer, phenytoin, was stopped. Case 2 was also very sensitive to CYP3A4 inducers as indicated by very low C/D ratios for carbamazepine, risperidone and paliperidone. The carbamazepine (2,800 mg/day) and risperidone (20 mg/day) dosages for this second patient are the highest doses ever seen for these drugs by the senior author. Risperidone induction appeared to last for many months and metabolism was definitively normal 3 years after stopping carbamazepine. On the other hand, olanzapine C/D ratios were normal for induction.

Conclusions:

The literature has never described similar cases of very high doses of drugs metabolized by CYP3A4. We speculate that these 2 patients may have unusual genetic profiles at the nuclear receptor levels; these receptors regulate induction of drugs.
RESUMEN
RESUMEN

Introducción:

Durante sus últimos 20 años de práctica, el último autor ha identificado estos 2 infrecuentes casos que necesitaban dosis extremadamente altas de medicaciones metabolizadas por el CYP3A4 para alcanzar y mantener concentraciones séricas terapéuticas.

Métodos:

La gran capacidad metabólica de estos 2 pacientes se demostró por los bajos cocientes entre concentración y dosis (C/D) de varias medicaciones metabolizadas por el CYP3A4.

Resultados:

El caso 1 se caracterizaba por una historia de altas dosis de carbamazepina (1.500 mg/día) y la necesidad de tomar 170 mg de diazepam en 2 días para facilitar una limpieza dental. La gran actividad de la isoenzima CYP3A4 se manifestó por una gran capacidad metabólica de quetiapina y diazepam, cuya normalización tardó más de 1 año tras la toma de un inductor, fenitoína. El caso 2 tambien era muy sensible a la inducción, lo cual se demuestra por los bajos cocientes C/D de carbamazepina, risperidona y paliperidona. Las dosis de carbamazepina (2.800 mg/día) y risperidona (20 mg/día) de este segundo paciente son las más altas nunca vistas por el último autor. La inducción de risperidona duró muchos meses y su metabolismo era normal 3 años después de interrumpir la carbamazepina. El cociente C/D de olanzapina era normal para la inducción.

Conclusiones:

Nunca se habían descrito casos similares de dosis tan altas de medicaciones metabolizadas por el CYP3A4. Se especula con que estos pacientes podrían tener unos perfiles genéticos inusuales en los receptores nucleares que regulan la inducción de medicamentos.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Pharmaceutical Preparations / Cytochrome P-450 CYP3A / Cytochrome P-450 CYP3A Inducers Type of study: Prognostic study Limits: Humans Language: English Journal: Rev. colomb. psiquiatr Journal subject: Psychiatry Year: 2020 Type: Article Affiliation country: Canada / China / United States Institution/Affiliation country: Capital Medical University/CN / Centre for Addiction and Mental Health/CA / Eastern State Hospital/US / Eastside Psychiatric Hospital/US

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Index: LILACS (Americas) Main subject: Pharmaceutical Preparations / Cytochrome P-450 CYP3A / Cytochrome P-450 CYP3A Inducers Type of study: Prognostic study Limits: Humans Language: English Journal: Rev. colomb. psiquiatr Journal subject: Psychiatry Year: 2020 Type: Article Affiliation country: Canada / China / United States Institution/Affiliation country: Capital Medical University/CN / Centre for Addiction and Mental Health/CA / Eastern State Hospital/US / Eastside Psychiatric Hospital/US