Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Sermsappasuk, Pakawadee, Chaiyakunapruk, Nathorn, Lohitnavy, Manupat and Kitiyakara, Chagriya (2013) Assessing clinical evidence of drug interactions between citrus juices and cyclosporine. Asian Biomedicine, 7 4: 477-489. doi:10.5372/1905-7415.0704.202

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Author Sermsappasuk, Pakawadee
Chaiyakunapruk, Nathorn
Lohitnavy, Manupat
Kitiyakara, Chagriya
Title Assessing clinical evidence of drug interactions between citrus juices and cyclosporine
Journal name Asian Biomedicine   Check publisher's open access policy
ISSN 1905-7415
Publication date 2013
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.5372/1905-7415.0704.202
Open Access Status
Volume 7
Issue 4
Start page 477
End page 489
Total pages 13
Place of publication Bangkok, Thailand
Publisher Chulalongkorn University * Faculty of Medicine
Collection year 2014
Language eng
Subject 2700 Medicine
1300 Biochemistry, Genetics and Molecular Biology
Formatted 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

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. 
Keyword Bioavailability
Citrus juice
Drug interaction
Meta analysis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2014 Collection
School of Public Health Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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