Clinical Therapeutics/Volume 34, Number 10, 2012Įffects of Grapefruit and Seville Orange Juices on the Pharmacokinetic Properties of Colchicine in Healthy Subjects However, the absence of a positive control in these studies dictates that caution should be used when applying these results clinically. Contrary to the expected effects of inhibiting the enzymes that metabolize colchicine, neither juice increased exposure to colchicine. Seville orange juice paradoxically reduced absorption of colchicine and increased Tmax, but the clinical significance of this is unknown. In contrast to label warnings based on the literature, grapefruit juice did not affect the pharmacokinetics of colchicine. There were no significant treatment-related AEs reported, and the most likely AEs were general gastrointestinal events. Colchicine in combination with grapefruit or Seville orange juice was well tolerated. Seville orange juice also caused, on average, a 1-hour delay in Tmax. When colchicine was administered with Seville orange juice, a moderate inhibitor, Cmax and AUC were decreased by ∼24% and ∼20%, respectively. Although it is considered to be a moderate concentration-dependent CYP3A4 inhibitor, grapefruit juice did not significantly affect the pharmacokinetic parameters of colchicine. AEs were coded according to corresponding MedDRA-coded system organ classes.įorty-four subjects received either grapefruit juice (72.7% male 90.9% white) or Seville orange juice (62.5% female 100% white). All subjects were monitored for adverse events (AEs) throughout the confinement portion of the study and were queried at the outpatient visits.
In each study, blood samples for pharmacokinetics were collected before dosing with colchicine and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose. Pharmacokinetic data were obtained following a single 0.6-mg dose of colchicine before the administration of juice and again following a single 0.6-mg dose of colchicine on the final day of juice administration. Undiluted juice (240 mL) was administered twice daily for 4 days. Healthy volunteers were enrolled in 2 open-label, Phase I studies. Two Phase I studies assessed the effects of multiple daily consumptions of Seville orange juice or grapefruit juice on the pharmacokinetic properties of colchicine in healthy volunteers. Severe toxicities in patients consuming these juices while taking other drugs metabolized through these pathways have been reported.
Two of the furocoumarins in grapefruit juice and Seville orange juice can inhibit intestinal cytochrome P450 (CYP) isozyme 3A4 and P-glycoprotein (involved in colchicine metabolism and transport). The labeling for colchicine (indicated for acute gout flares or prophylaxis) includes strict advisories regarding drug–drug and drug–food interactions, including warnings against consuming grapefruit or grapefruit juice during treatment. Abstract of research paper on Clinical medicine, author of scientific article - Suman Wason, Jennifer L.
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