Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations
Tacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the cha...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/11/10/1205 |
| _version_ | 1797550853118230528 |
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| author | Teun van Gelder Oumaima Etsouli Dirk Jan Moes Jesse J. Swen |
| author_facet | Teun van Gelder Oumaima Etsouli Dirk Jan Moes Jesse J. Swen |
| author_sort | Teun van Gelder |
| collection | DOAJ |
| description | Tacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the changes in drug exposure are larger in patients who express the CYP3A5 enzyme (<i>CYP3A5 *1/*3 or *1/*1</i>) compared to nonexpressers (<i>CYP3A5*3/*3</i>). Possibly, these differences are due to the fact that in the upper region of the small intestine CYP3A activity is higher, and that this expression of CYP3A decreases towards the more distal parts of the gut. Modified release formulations may therefore be subject to a less presystemic metabolism. However, the full implications of pharmacogenetic variants affecting the expression and function of drug transporters in the gut wall and of enzymes involved in phase I and phase II metabolism on the different formulations are incompletely understood, and additional studies are required. Conclusions: In all patients in whom the formulation of tacrolimus is changed, drug levels need to be checked to avoid clinically relevant under- or overexposure. In patients with the <i>CYP3A5</i> expresser genotype, this recommendation is even more important, as changes in drug exposure can be expected. |
| first_indexed | 2024-03-10T15:35:22Z |
| format | Article |
| id | doaj.art-41ce088ec25f4672b9a0b5c16713e83f |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T15:35:22Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
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| spelling | doaj.art-41ce088ec25f4672b9a0b5c16713e83f2023-11-20T17:14:49ZengMDPI AGGenes2073-44252020-10-011110120510.3390/genes11101205Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus FormulationsTeun van Gelder0Oumaima Etsouli1Dirk Jan Moes2Jesse J. Swen3Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The NetherlandsDepartment of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The NetherlandsDepartment of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The NetherlandsDepartment of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The NetherlandsTacrolimus-modified release formulations allow for once-daily dosing, and adherence is better compared to the twice-daily immediate release formulation. When patients are switched from one formulation to another, variable changes in drug concentrations are observed. Current data suggest that the changes in drug exposure are larger in patients who express the CYP3A5 enzyme (<i>CYP3A5 *1/*3 or *1/*1</i>) compared to nonexpressers (<i>CYP3A5*3/*3</i>). Possibly, these differences are due to the fact that in the upper region of the small intestine CYP3A activity is higher, and that this expression of CYP3A decreases towards the more distal parts of the gut. Modified release formulations may therefore be subject to a less presystemic metabolism. However, the full implications of pharmacogenetic variants affecting the expression and function of drug transporters in the gut wall and of enzymes involved in phase I and phase II metabolism on the different formulations are incompletely understood, and additional studies are required. Conclusions: In all patients in whom the formulation of tacrolimus is changed, drug levels need to be checked to avoid clinically relevant under- or overexposure. In patients with the <i>CYP3A5</i> expresser genotype, this recommendation is even more important, as changes in drug exposure can be expected.https://www.mdpi.com/2073-4425/11/10/1205tacrolimuspharmacokineticsCYP3Aimmediate releasemodified releaseswitching |
| spellingShingle | Teun van Gelder Oumaima Etsouli Dirk Jan Moes Jesse J. Swen Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations Genes tacrolimus pharmacokinetics CYP3A immediate release modified release switching |
| title | Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations |
| title_full | Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations |
| title_fullStr | Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations |
| title_full_unstemmed | Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations |
| title_short | Comparison of the Impact of Pharmacogenetic Variability on the PK of Slow Release and Immediate Release Tacrolimus Formulations |
| title_sort | comparison of the impact of pharmacogenetic variability on the pk of slow release and immediate release tacrolimus formulations |
| topic | tacrolimus pharmacokinetics CYP3A immediate release modified release switching |
| url | https://www.mdpi.com/2073-4425/11/10/1205 |
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