Please use this identifier to cite or link to this item: https://doi.org/10.1007/s13318-018-0531-5
Title: CONVERSION FROM TWICE-DAILY PROGRAF<SUP>®</SUP> TO ONCE-DAILY ADVAGRAF<SUP>®</SUP> IN MULTI-ETHNIC ASIAN ADULT RENAL TRANSPLANT RECIPIENTS WITH OR WITHOUT CONCOMITANT USE OF DILTIAZEM: IMPACT OF CYP3A5 AND MDR1 GENETIC POLYMORPHISMS ON TACROLIMUS EXPOSURE
Authors: Yau, WP 
Loh, CWT
Vathsala, A 
Keywords: 1117 Public Health and Health Services
Clinical
Public Health
6.1 Pharmaceuticals
Issue Date: 1-Jan-2018
Publisher: Springer Nature
Citation: Yau, WP, Loh, CWT, Vathsala, A (2018-01-01). CONVERSION FROM TWICE-DAILY PROGRAF® TO ONCE-DAILY ADVAGRAF® IN MULTI-ETHNIC ASIAN ADULT RENAL TRANSPLANT RECIPIENTS WITH OR WITHOUT CONCOMITANT USE OF DILTIAZEM: IMPACT OF CYP3A5 AND MDR1 GENETIC POLYMORPHISMS ON TACROLIMUS EXPOSURE 100 (7S) : S714-S714. ScholarBank@NUS Repository. https://doi.org/10.1007/s13318-018-0531-5
Abstract: © 2018, Springer Nature Switzerland AG. Background and Objectives: Tacrolimus is the mainstay of immunosuppression in renal transplantation. Given that once-daily administration improves patient compliance, 1:1 dose conversion from twice-daily Prograf® to once-daily Advagraf® is recommended. Although cytochrome P450 (CYP) 3A5 and multi-drug resistance 1 (MDR1) polymorphisms influence tacrolimus concentrations, it is unknown if these impact on conversion. This study investigated the change in the pharmacokinetics of tacrolimus after conversion from Prograf® to Advagraf® and examined the impact of CYP3A5 and MDR1 C3435T polymorphisms on those pharmacokinetics. Methods: A prospective open-label pharmacokinetic study of 1:1 conversion from Prograf® to Advagraf® with or without diltiazem was conducted on 26 stable renal transplant recipients. Blood samples were collected over 24 h during each phase, tacrolimus concentrations were assayed, and noncompartmental pharmacokinetic analysis was performed. All participants were genotyped for CYP3A5*3 and MDR1 C3435T. Results: After conversion, without diltiazem, the area under the concentration–time curve at steady state from 0 to 24 h after dose administration (AUCss, 0–24) was significantly reduced [median 224 (range 172–366) vs. 184 (104–347) ng·h/mL, p = 0.006, n = 26]. A decrease in tacrolimus exposure (median 21%) was only evident among CYP3A5 expressors [227 (172–366) vs. 180 (104–347) ng·h/mL, p = 0.014, n = 18], not among non-expressors [215 (197–290) vs. 217 (129–281) ng·h/mL, p = 0.263, n = 8]. In contrast, among CYP3A5 expressors receiving diltiazem, AUCss, 0–24 did not change significantly upon conversion [229 (170–296) vs. 221 (123–342) ng·h/mL, p = 0.575, n = 10]. An independent effect was not evident for MDR1 C3435T polymorphism. Conclusion: The high prevalence of CYP3A5 polymorphism among Asians may lead to a significant reduction in tacrolimus exposure with 1:1 dose conversion of Prograf® to Advagraf®. These results advocate for CYP3A5 determination prior to conversion, and suggest that 1:1.25 conversion should be used for CYP3A5 expressors and 1:1 conversion for other patients.
URI: https://scholarbank.nus.edu.sg/handle/10635/155312
ISSN: 0378-7966
2107-0180
DOI: 10.1007/s13318-018-0531-5
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