Analysis of Combined Effect of CYP2C19 Genetic Polymorphism and Proton Pump Inhibitors Coadministration on through concentration of Voriconazole
| dc.contributor.author | Mafuru, Magesa | |
| dc.contributor.author | Phillip, Amani | |
| dc.contributor.author | Mgone, Charles S. | |
| dc.date.accessioned | 2022-01-26T10:45:46Z | |
| dc.date.available | 2022-01-26T10:45:46Z | |
| dc.date.issued | 2021 | |
| dc.description.abstract | Purpose: To analyze the combined effect of CYP2C19 genetic polymorphism and PPIs coadministration on voriconazole trough concentration (VCZ-Ctrough) in Chinese patients with hematological disorders. Patients and Methods: A prospective observational study involved 250 plasma samples from 114 adult patients receiving voriconazole with or without PPIs were analyzed. Demographics and clinical characteristics were obtained from patient’s records. A validated LC-MS/MS was used to quantify the plasma VCZ-Ctrough. Genotyping for CYP2C19*2 and CYP2C19*3 variant alleles was performed by PCR-RFLP followed by DNA sequencing. The combined total score (from 2 to 5) was calculated for each patient. The higher the score, the lesser the metabolism of the patient. Findings: Fifty percent of patients administered with voriconazole were coadministered with PPIs, predominantly omeprazole or esomeprazole. Patients exhibiting CYP2C19 poor metabolizer phenotype showed a significantly higher median VCZ-Ctrough, (4.31µg/mL [IQR, 1.64µg/mL–7.36µg/mL]) than patients with normal metabolizer (1.38µg/mL, [IQR, 0.79µg/mL–2.14µg/mL], p < 0.0001). Similarly, patients co-administration with PPIs had higher median VCZ-Ctrough (2.86µg/mL [IQR 1.33µg/mL–4.66µg/mL]), than PPIs non-users (1.71µg/mL, [IQR, 0.86µg/mL–3.48µg/mL], p = 0.001). However, we noted that the median VCZ-Ctrough for each factor was ranging within the normal recommended therapeutic range in the Chinese population (0.5µg/mL–5µg/mL). But when the two factors were combined, the median VCZ-Ctrough was steadily increasing as the metabolic capacity (reflected by combined total score) was increasing. Importantly, the median VCZ-Ctrough in PM/PPIs user (total score 5) was significantly elevated to supra-therapeutic levels compared to NM/PPI non-user group (total score 2) (5.83µg/mL [IQR, 2.19µg/mL–9.51µg/mL] versus 1.13µg/mL [IQR, 0.67µg/mL–1.82µg/mL]), respectively, P < 0.0001. Furthermore, we observed that the elevation of median VCZ-Ctrough to supra-therapeutic levels was largely contributed by omeprazole or esomeprazole compared to lansoprazole or pantoprazole. Conclusion: Coadministration with PPIs significantly increased voriconazole trough concentrations and there was an additive effect in CYP2C19 PMs, who were most likely to have supra-therapeutic levels. | en_US |
| dc.identifier.citation | Mafuru, M., Wu, S., Mayala, H., Msengwa, Z., Phillip, A. and Mgone, C., 2021. Analysis of Combined Effect of CYP2C19 Genetic Polymorphism and Proton Pump Inhibitors Coadministration on Trough Concentration of Voriconazole. Pharmacogenomics and Personalized Medicine, 14, p.1379. | en_US |
| dc.identifier.other | doi: 10.2147/PGPM.S329662 | |
| dc.identifier.uri | http://hdl.handle.net/123456789/878 | |
| dc.language.iso | en | en_US |
| dc.publisher | Pharmacogenomics and Personalized Medicine | en_US |
| dc.subject | CYP2C19 polymorphism, | en_US |
| dc.subject | Voriconazole | en_US |
| dc.subject | Proton pump inhibitors | en_US |
| dc.title | Analysis of Combined Effect of CYP2C19 Genetic Polymorphism and Proton Pump Inhibitors Coadministration on through concentration of Voriconazole | en_US |
| dc.type | Article | en_US |