<abstract xmlns="http://www.w3.org/1999/xhtml"> Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine; however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other types of citrus juice on oral bioavailability of cyclosporine in humans using meta-analysis.Methods: We conducted a meta-analysis of placebo-controlled studies evaluating the effects of citrus juices on bioavailability of cyclosporine. The studies were identified in PubMed, Cochrane CENTRAL, CINAHL, ISI Web of Knowledge, Psych Info International, Pharmaceutical Abstract (IPA), and reference lists of relevant papers. The weighted-mean difference (WMD) was calculated for net changes in the area under the curve (AUC) of cyclosporine. All studies conducted as placebo-controlled crossover studies in humans to compare the effect of citrus juices and control (drinking water) on AUC of cyclosporine and/or Cmin,ss were reviewed. All studies included were evaluated and extracted independently, and discrepancies were resolved through discussion.Results: Eighteen studies were identified. A subgroup analysis suggested that grapefruit juice significantly increased AUC of cyclosporine (WMD = 1762.5 ng⋅h/ml, 95%CI = 1178.9-2346.0 ng⋅h/ml, p &lt; 0.001). While a meta-analysis of all other types of citrus juices (tangerine juice, Seville orange juice, sweet orange juice, and citrus soda) except pomelo juice revealed no effect on the AUC of cyclosporine (WMD = -181.0 ng⋅h/ml, 95%CI = -582.8-220.9 ng⋅h/ml, p > 0.5), a study of pomelo juice indicated a significant increase in the AUC of cyclosporine.Conclusions: Grapefruit juice intake increases oral bioavailability of cyclosporine in both healthy volunteers and renal transplant patients, whereas all other types of citrus juices may not have an influence on the oral bioavailability of cyclosporine. Current evidence suggests that pomelo juice may be able to increase cyclosporine oral bioavailability.</abstract>

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine; however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other types of citrus juice on oral bioavailability of cyclosporine in humans using meta-analysis.Methods: We conducted a meta-analysis of placebo-controlled studies evaluating the effects of citrus juices on bioavailability of cyclosporine. The studies were identified in PubMed, Cochrane CENTRAL, CINAHL, ISI Web of Knowledge, Psych Info International, Pharmaceutical Abstract (IPA), and reference lists of relevant papers. The weighted-mean difference (WMD) was calculated for net changes in the area under the curve (AUC) of cyclosporine. All studies conducted as placebo-controlled crossover studies in humans to compare the effect of citrus juices and control (drinking water) on AUC of cyclosporine and/or Cmin,ss were reviewed. All studies included were evaluated and extracted independently, and discrepancies were resolved through discussion.Results: Eighteen studies were identified. A subgroup analysis suggested that grapefruit juice significantly increased AUC of cyclosporine (WMD = 1762.5 ng⋅h/ml, 95%CI = 1178.9-2346.0 ng⋅h/ml, p < 0.001). While a meta-analysis of all other types of citrus juices (tangerine juice, Seville orange juice, sweet orange juice, and citrus soda) except pomelo juice revealed no effect on the AUC of cyclosporine (WMD = -181.0 ng⋅h/ml, 95%CI = -582.8-220.9 ng⋅h/ml, p > 0.5), a study of pomelo juice indicated a significant increase in the AUC of cyclosporine.Conclusions: Grapefruit juice intake increases oral bioavailability of cyclosporine in both healthy volunteers and renal transplant patients, whereas all other types of citrus juices may not have an influence on the oral bioavailability of cyclosporine. Current evidence suggests that pomelo juice may be able to increase cyclosporine oral bioavailability.

Review article. Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Center of Pharmaceutical Outcomes Research (CPOR), Naresuan University, Phitsanulok 65000, Thailand,

Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand,

Center of Excellence for Environmental Health and Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000,

School of Population Health, University of Queensland, Brisbane, Australia,

School of Pharmacy, University of Wisconsin, Madison,

Lohitnavy aCenter of Pharmaceutical Outcomes Research (CPOR), Naresuan University, Phitsanulok 65000, Thailand,

Pharmacokinetic Research Unit, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand,

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400,

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine; however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other types of citrus juice on oral bioavailability of cyclosporine in humans using meta-analysis.Methods: We conducted a meta-analysis of placebo-controlled studies evaluating the effects of citrus juices on bioavailability of cyclosporine. The studies were identified in PubMed, Cochrane CENTRAL, CINAHL, ISI Web of Knowledge, Psych Info International, Pharmaceutical Abstract (IPA), and reference lists of relevant papers. The weighted-mean difference (WMD) was calculated for net changes in the area under the curve (AUC) of cyclosporine. All studies conducted as placebo-controlled crossover studies in humans to compare the effect of citrus juices and control (drinking water) on AUC of cyclosporine and/or Cmin,ss were reviewed. All studies included were evaluated and extracted independently, and discrepancies were resolved through discussion.Results: Eighteen studies were identified. A subgroup analysis suggested that grapefruit juice significantly increased AUC of cyclosporine (WMD = 1762.5 ng⋅h/ml, 95%CI = 1178.9-2346.0 ng⋅h/ml, p  0.5), a study of pomelo juice indicated a significant increase in the AUC of cyclosporine.Conclusions: Grapefruit juice intake increases oral bioavailability of cyclosporine in both healthy volunteers and renal transplant patients, whereas all other types of citrus juices may not have an influence on the oral bioavailability of cyclosporine. Current evidence suggests that pomelo juice may be able to increase cyclosporine oral bioavailability.

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine; however, the results from the literature...

Review article. Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Published Online: Feb 04, 2017

Page range: 477 - 489

DOI: https://doi.org/10.5372/1905-7415.0704.202

Keywords
Bioavailability, citrus juice, cyclosporine, drug interaction, meta-analysis

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Review article. Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Published Online: Feb 04, 2017

Page range: 477 - 489

DOI: https://doi.org/10.5372/1905-7415.0704.202

KeywordsBioavailability, citrus juice, cyclosporine, drug interaction, meta-analysis

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Keywords
Bioavailability, citrus juice, cyclosporine, drug interaction, meta-analysis