The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis
Propafenone (PPF) is a class 1C antiarrhythmic agent mainly metabolized by cytochrome (CYP) 2D6, CYP1A2, and CYP3A4. Previous studies have shown that CYP2D6 polymorphism influences the pharmacokinetics (PK) of PPF. However, the small sample sizes of PK studies can lead to less precise estimates of t...
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1446 |
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| author | Quyen Thi Tran In-hwan Baek Na-young Han Hwi-yeol Yun Jung-woo Chae |
| author_facet | Quyen Thi Tran In-hwan Baek Na-young Han Hwi-yeol Yun Jung-woo Chae |
| author_sort | Quyen Thi Tran |
| collection | DOAJ |
| description | Propafenone (PPF) is a class 1C antiarrhythmic agent mainly metabolized by cytochrome (CYP) 2D6, CYP1A2, and CYP3A4. Previous studies have shown that CYP2D6 polymorphism influences the pharmacokinetics (PK) of PPF. However, the small sample sizes of PK studies can lead to less precise estimates of the PK parameters. Thus, this meta-analysis was performed to merge all current PK studies of PPF to determine the effects of the CYP2D6 phenotype more accurately on the PPF PK profile. We searched electronic databases for published studies to investigate the association between the PPF PK and CYP2D6 phenotype. Four PK-related outcomes were included: area under the time–concentration curve (AUC), maximum concentration (C<sub>max</sub>), apparent clearance (CL/F), and half-life (t<sub>1/2</sub>). A total of five studies were included in this meta-analysis (<i>n</i> = 56). Analyses were performed to compare PK parameters between poor metabolizers (PMs) versus extensive metabolizers (EMs). PPF has a non-linear pharmacokinetics; therefore, analyses were performed according to dose (300 mg and 400 mg). At 300 mg, the AUC mean (95% CI), C<sub>max</sub>, and t<sub>1/2</sub> of PPF in PMs were 15.9 (12.5–19.2) µg·h/mL, 1.10 (0.796–1.40) µg/mL, and 12.8 (11.3–14.3) h, respectively; these values were 2.4-, 11.2-, and 4.7-fold higher than those in the EM group, respectively. At 400 mg, a comparison was performed between S- and R-enantiomers. The CL/F was approximately 1.4-fold higher for the R-form compared with the S-form, which was a significant difference. This study demonstrated that CYP2D6 metabolizer status could significantly affect the PPF PK profile. Adjusting the dose of PPF according to CYP2D6 phenotype would help to avoid adverse effects and ensure treatment efficacy. |
| first_indexed | 2024-03-09T13:11:08Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T13:11:08Z |
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| spelling | doaj.art-ef9ee42fe42049c1a5fefc7ff02295012023-11-30T21:42:06ZengMDPI AGPharmaceutics1999-49232022-07-01147144610.3390/pharmaceutics14071446The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-AnalysisQuyen Thi Tran0In-hwan Baek1Na-young Han2Hwi-yeol Yun3Jung-woo Chae4College of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Kyungsung University, Busan 48434, KoreaCollege of Pharmacy, Jeju National University, Jeju 63243, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaPropafenone (PPF) is a class 1C antiarrhythmic agent mainly metabolized by cytochrome (CYP) 2D6, CYP1A2, and CYP3A4. Previous studies have shown that CYP2D6 polymorphism influences the pharmacokinetics (PK) of PPF. However, the small sample sizes of PK studies can lead to less precise estimates of the PK parameters. Thus, this meta-analysis was performed to merge all current PK studies of PPF to determine the effects of the CYP2D6 phenotype more accurately on the PPF PK profile. We searched electronic databases for published studies to investigate the association between the PPF PK and CYP2D6 phenotype. Four PK-related outcomes were included: area under the time–concentration curve (AUC), maximum concentration (C<sub>max</sub>), apparent clearance (CL/F), and half-life (t<sub>1/2</sub>). A total of five studies were included in this meta-analysis (<i>n</i> = 56). Analyses were performed to compare PK parameters between poor metabolizers (PMs) versus extensive metabolizers (EMs). PPF has a non-linear pharmacokinetics; therefore, analyses were performed according to dose (300 mg and 400 mg). At 300 mg, the AUC mean (95% CI), C<sub>max</sub>, and t<sub>1/2</sub> of PPF in PMs were 15.9 (12.5–19.2) µg·h/mL, 1.10 (0.796–1.40) µg/mL, and 12.8 (11.3–14.3) h, respectively; these values were 2.4-, 11.2-, and 4.7-fold higher than those in the EM group, respectively. At 400 mg, a comparison was performed between S- and R-enantiomers. The CL/F was approximately 1.4-fold higher for the R-form compared with the S-form, which was a significant difference. This study demonstrated that CYP2D6 metabolizer status could significantly affect the PPF PK profile. Adjusting the dose of PPF according to CYP2D6 phenotype would help to avoid adverse effects and ensure treatment efficacy.https://www.mdpi.com/1999-4923/14/7/1446propafenonepharmacokineticsphenotypeCYP2D6precision medicine |
| spellingShingle | Quyen Thi Tran In-hwan Baek Na-young Han Hwi-yeol Yun Jung-woo Chae The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis Pharmaceutics propafenone pharmacokinetics phenotype CYP2D6 precision medicine |
| title | The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis |
| title_full | The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis |
| title_fullStr | The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis |
| title_short | The Effect of CYP2D6 Phenotypes on the Pharmacokinetics of Propafenone: A Systematic Review and Meta-Analysis |
| title_sort | effect of cyp2d6 phenotypes on the pharmacokinetics of propafenone a systematic review and meta analysis |
| topic | propafenone pharmacokinetics phenotype CYP2D6 precision medicine |
| url | https://www.mdpi.com/1999-4923/14/7/1446 |
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