Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals
| Autor: | Edward M Russak, Edward M. Bednarczyk |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Tetrabenazine
chemistry.chemical_element 030204 cardiovascular system & hematology 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Chorea Toxicity Tests Humans Tardive Dyskinesia Molecule Medicine Pharmacology (medical) Drug Approval Isotope United States Food and Drug Administration business.industry Radiochemistry Deuterium Legislation Drug United States Huntington Disease Pharmaceutical Preparations Isotopes of hydrogen Drug development chemistry Deutetrabenazine business Carbon |
| Zdroj: | Annals of Pharmacotherapy. 53:211-216 |
| ISSN: | 1542-6270 1060-0280 |
| Popis: | Objective: Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine (Austedo, Teva Pharmaceutical Industries, Ltd) is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington’s disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools. Data Sources: A search of the MEDLINE (1946 to present) database was undertaken using the Ovid interface. The search was conducted using the heading deuterium and then limited to Administration & Dosage, Adverse Effects, Pharmacokinetics, Pharmacology, Poisoning, Therapeutic Use, and Toxicity. Study Selection and Data Extraction: All articles were reviewed and those with human information were included. Review articles were likewise interrogated for additional published human data. Conclusions: Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities. |
| Databáze: | OpenAIRE |
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