| Title |
Rosiglitazone Metabolism in Human Liver Microsomes Using a Substrate Depletion Method
|
|---|---|
| Published in |
Drugs in R&D, January 2017
|
| DOI | 10.1007/s40268-016-0166-4 |
| Pubmed ID | |
| Authors |
Maryam Bazargan, David J. R. Foster, Andrew K. Davey, Beverly S. Muhlhausler |
| Abstract |
Elimination of rosiglitazone in humans is via hepatic metabolism. The existing studies suggest that CYP2C8 is the major enzyme responsible, with a minor contribution from CYP2C9; however, other studies suggest the involvement of additional cytochrome P450 enzymes and metabolic pathways. Thus a full picture of rosiglitazone metabolism is unclear. This study aimed to improve the current understanding of potential drug-drug interactions and implications for therapy by evaluating the kinetics of rosiglitazone metabolism and examining the impact of specific inhibitors on its metabolism using the substrate depletion method. In vitro oxidative metabolism of rosiglitazone in human liver microsomes obtained from five donors was determined over a 0.5-500 µM substrate range including the contribution of CYP2C8, CYP2C9, CYP3A4, CYP2E1, and CYP2D6. The maximum reaction velocity was 1.64 ± 0.98 nmol·mg(-1)·min(-1). The CYP2C8 (69 ± 20%), CYP2C9 (42 ± 10%), CYP3A4 (52 ± 23%), and CEP2E1 (41 ± 13%) inhibitors all significantly inhibited rosiglitazone metabolism. The results suggest that other cytochrome P450 enzymes, including CYP2C9, CYP3A4, and CEP2E1, in addition to CYP28, also play an important role in the metabolism of rosiglitazone. This example demonstrates that understanding the complete metabolism of a drug is important when evaluating the potential for drug-drug interactions and will assist to improve the current therapeutic strategies. |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 4 | 17% |
| Student > Master | 3 | 13% |
| Lecturer | 1 | 4% |
| Student > Doctoral Student | 1 | 4% |
| Other | 1 | 4% |
| Other | 4 | 17% |
| Unknown | 9 | 39% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 35% |
| Biochemistry, Genetics and Molecular Biology | 2 | 9% |
| Unspecified | 1 | 4% |
| Chemical Engineering | 1 | 4% |
| Nursing and Health Professions | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 9 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 March 2017.
All research outputs
#20,407,586
of 22,957,478 outputs
Outputs from Drugs in R&D
#304
of 330 outputs
Outputs of similar age
#356,895
of 421,788 outputs
Outputs of similar age from Drugs in R&D
#11
of 11 outputs
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So far Altmetric has tracked 330 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.