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.
Translated title of the contribution | High Doses of Drugs Extensively Metabolized by CYP3A4 Were Needed to Reach Therapeutic Concentrations in Two Patients Taking Inducers |
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Original language | Spanish |
Pages (from-to) | 84-95 |
Number of pages | 12 |
Journal | Revista Colombiana de Psiquiatria |
Volume | 49 |
Issue number | 2 |
DOIs | |
State | Published - Apr 1 2020 |
Bibliographical note
Funding Information:The authors acknowledge Lorraine Maw, M.A. who helped in editing this article. Kay Marshall, who was at that time Lab Director at the psychiatric hospital, and her staff were very helpful with the collection and analyses of the blood samples during several years of treating the first patient. Georgios Schoretsanitis, MD, from the University Hospital of Psychiatry, Bern, Switzerland, helped with the translation from German to English of Reference 68.
Publisher Copyright:
© 2018 Asociación Colombiana de Psiquiatría
Keywords
- Carbamazepine
- Diazepam
- Drug interactions
- Enzymes
- Induction
- Quetiapine
- Risperidone
ASJC Scopus subject areas
- Psychiatry and Mental health