The emerging role of cytochrome P450 3A in psychopharmacology

T. A. Ketter, D. A. Flockhart, R. M. Post, K. Denicoff, P. J. Pazzaglia, L. B. Marangell, M. S. George, A. M. Callahan

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Recent advances in molecular pharmacology have allowed the characterization of the specific isoforms that mediate the metabolism of various medications. This information can be integrated with older clinical observations to begin to develop specific mechanistic and predictive models of psychotropic drug interactions. The polymorphic cytochrome p450 2D6 has gained much attention, because competition for this isoform is responsible for serotonin reuptake inhibitor-induced increases in tricyclic antidepressant concentrations in plasma. However, the cytochrome p450 3A subfamily and the 3A3 and 3A4 isoforms (CYP3A3/4) in particular are becoming increasingly important in psychopharmacology as a result of their central involvement in the metabolism of a wide range of steroids and medications, including antidepressants, benzodiazepines, calcium channel blockers, and carbamazepine. The inhibition of CYP3A3/4 by medications such as certain newer antidepressants, calcium channel blockers, and antibiotics can increase the concentrations of CYP3A3/4 substrates, yielding toxicity. The induction of CYP3A3/4 by medications such as carbamazepine can decrease the concentrations of CYP3A3/4 substrates, yielding inefficiency. Thus, knowledge of the substrates, inhibitors, and inducers of CYP3A3/4 and other cytochrome p450 isoforms may help clinicians to anticipate and avoid pharmacokinetic drug interactions and improve rational prescribing practices.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalJournal of Clinical Psychopharmacology
Volume15
Issue number6
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Psychopharmacology
Protein Isoforms
Carbamazepine
Calcium Channel Blockers
Drug Interactions
Antidepressive Agents
Cytochrome P-450 CYP2D6
Tricyclic Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Benzodiazepines
Cytochrome P-450 Enzyme System
Pharmacokinetics
Steroids
Pharmacology
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Ketter, T. A., Flockhart, D. A., Post, R. M., Denicoff, K., Pazzaglia, P. J., Marangell, L. B., ... Callahan, A. M. (1995). The emerging role of cytochrome P450 3A in psychopharmacology. Journal of Clinical Psychopharmacology, 15(6), 387-398. https://doi.org/10.1097/00004714-199512000-00002

The emerging role of cytochrome P450 3A in psychopharmacology. / Ketter, T. A.; Flockhart, D. A.; Post, R. M.; Denicoff, K.; Pazzaglia, P. J.; Marangell, L. B.; George, M. S.; Callahan, A. M.

In: Journal of Clinical Psychopharmacology, Vol. 15, No. 6, 1995, p. 387-398.

Research output: Contribution to journalArticle

Ketter, TA, Flockhart, DA, Post, RM, Denicoff, K, Pazzaglia, PJ, Marangell, LB, George, MS & Callahan, AM 1995, 'The emerging role of cytochrome P450 3A in psychopharmacology', Journal of Clinical Psychopharmacology, vol. 15, no. 6, pp. 387-398. https://doi.org/10.1097/00004714-199512000-00002
Ketter TA, Flockhart DA, Post RM, Denicoff K, Pazzaglia PJ, Marangell LB et al. The emerging role of cytochrome P450 3A in psychopharmacology. Journal of Clinical Psychopharmacology. 1995;15(6):387-398. https://doi.org/10.1097/00004714-199512000-00002
Ketter, T. A. ; Flockhart, D. A. ; Post, R. M. ; Denicoff, K. ; Pazzaglia, P. J. ; Marangell, L. B. ; George, M. S. ; Callahan, A. M. / The emerging role of cytochrome P450 3A in psychopharmacology. In: Journal of Clinical Psychopharmacology. 1995 ; Vol. 15, No. 6. pp. 387-398.
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