Details of Drug-Drug Interaction
| Drug General Information (ID: DDI6LH87WF) | |||||||||
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| Drug Name | Dolasetron | Drug Info | Glycerol phenylbutyrate | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antiemetics | Urea Cycle Disorder Agents | |||||||
| Structure | |||||||||
| Mechanism of Dolasetron-Glycerol phenylbutyrate Interaction (Severity Level: Moderate) | |||||||||
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| CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph | |||||||||
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| Drug Name | Dolasetron | Glycerol phenylbutyrate | |||||||
| Mechanism | CYP450 2D6 substrate | CYP450 2D6 inhibitor | |||||||
| Key Mechanism Factor 1 | |||||||||
| Factor Name | Cytochrome P450 2D6 |
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Structure
Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
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| Gene Name | CYP2D6 | ||||||||
| Uniprot ID | CP2D6_HUMAN | ||||||||
| KEGG Pathway | hsa:1565 | ||||||||
| Protein Family | Cytochrome P450 family | ||||||||
| Protein Function |
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
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| Mechanism Description |
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| Recommended Action | |||||||||
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| Management | Caution is recommended if glycerol phenylbutyrate is administered with medicines that are substrates of CYP450 2D6, such as codeine, dextromethorphan, and some beta blockers (including metoprolol, carvedilol, labetalol, propranolol, and nebivolol). Dosage adjustments as well as clinical and laboratory monitoring may be appropriate. | ||||||||
| References | |||||||||||||||||||
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| 1 | Cerner Multum, Inc. "UK Summary of Product Characteristics.". | ||||||||||||||||||
| 2 | Product Information. Ravicti (glycerol phenylbutyrate). Hyperion Therapeutics Inc, South San Francisco, CA. | ||||||||||||||||||