ArticleEvidence-based complementary and alternative medicine : eCAM2011
Different influences on tacrolimus pharmacokinetics by coadministrations of zhi ke and zhi shi in rats.
Article in Evidence-based complementary and alternative medicine : eCAM, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Assessment of the Intestinal CYP3A Contribution to Drug Interactions with Extended-Release Tacrolimus (LCPT) Using Grapefruit Juice.Clinical pharmacology in drug development · 2026Trial
- Network Analysis of the Herb-Drug Interactions of Citrus Herbs Inspired by the "Grapefruit Juice Effect".ACS omega · 2022Article
- Reversion of p-glycoprotein-mediated multidrug resistance in human leukemic cell line by diallyl trisulfide.Evidence-based complementary and alternative medicine : eCAM · 2012Article
- Evaluation of chinese-herbal-medicine-induced herb-drug interactions: focusing on organic anion transporter 1.Evidence-based complementary and alternative medicine : eCAM · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the C(max) and AUC(0-t) of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.