Summary
The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males.
Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol · l−1, and in the AUC from 23 to 65 nmol · h · l−1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs.
The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (−9%) than did water (0%).
Similar content being viewed by others
References
Saltiel E, Gray Ellrodt A, Monk JP, Langley MS (1988) Felodipine: A review of its pharmacodynamic and pharmacokinetic properties, therapeutic use in hypertension. Drugs 36: 387–428
Edgar B (1988) Clinical pharmacokinetics of felodipine. Thesis, Göteborg
Bäärnhielm C, Hansson G (1986) Oxidation of 1,4-dihydropyridines of prostaglandin synthase and the peroxidic function of cytochrome P-450. Demonstration of a free radicale intermediate. Biochem Pharmacol 35: 1419–1425
Guengerich PF, Müller-Enoch D, Blair IA (1986) Oxidation of quinidine by human liver cytochrome P-450. Mol Pharmacol 30: 287–295
Bailey DG, Spence JD, Munoz C, Arnold JMO (1991) The interaction of citrus juices with felodipine and nifedipine. Lancet 337: 268–269
Pierpoint WS (1986) Flavonoids in the human diet. In: Plant flavonoids in biology and medicine: biochemical pharmacological and structure-activity relationships, Alan R. Liss Inc. pp 125–140
Wood AW, Smith DS, Chang RL, Huang M-T, Conney AH (1986) Effects of flavonoids on the metabolism of xenobiotics. In: Plant flavonoids in biology and medicine: biochemical pharmacological and structure-activity relationships. Alan R. Liss Inc pp 195–210
Ahnoff M (1984) Determination of felodipine in plasma by capillary gas chromatography with electron capture detection. J Pharm Biomed Analysis 2: 519–526
Edgar B, Lundborg P, Reg»rdh CG (1987) Clinical pharmacokinetics of felodipine. A summary. Drugs 34 [Suppl 3]: 16–27
Melander A, Lálka D and Mclean A (1988) Influence of food on the presystemic metabolism of drugs. Pharmacol Ther 38: 253–267
Guengerich FP, Brian WR, Iwasaki M, Sari M-A, Bäärnhielm C, Berntsson P (1991) Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450IIIA4. J Med Chem 34: 1838–1844
Kühnau J (1976) The flavonoids. A class of semi-essential food components: Their role in human nutrition. Wld Rev Nutr Diet 24: 117–191
Buening MK, Chang RL, Huang M-T, Fortner JG, Wood AW, Conney AH (1981) Activation and inhibition of benzo(a)pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids. Cancer Res 41: 67–72
Sousa RL and Marletta MA (1985) Inhibition of cytochrome P-450 activity in rat liver microsomes by the naturally occurring flavonoid, quercetin. Arch Biochem Biophys 240: 345–357
Guengerich P, Klein DM (1990) In vitro inhibition of dihydropyridine oxidation and aflatoxin B activation in human liver microsomes by naringenin and other flavonoids. Carcinogenesis II: 2276–2279
Edgar B, Bailey DG, Bergstrand R, Johnsson G and Lurje L (1990) Formulation dependent interaction between felodipine and grapefruit juice. Clin Pharmacol Ther 47 [Suppl]: 181
Abrahamsson B, Alpsten M, Hugosson M, Tölli J, Åberg J (1989) A combined gastro-intestinal transit and absorption study on felodipine extended release tablets. Eur J Clin Pharmacol 36 [Suppl]: A95 (Abstract OP34.03)
Soons P, Vogels B, Roosemalen N, Schoemaker H, Uchida, Edgar B, Lundahl J, Cohen A, Breimer D (1991) Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in man. Clin Pharmacol Ther 50: 394–403
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Edgar, B., Bailey, D., Bergstrand, R. et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine — and its potential clinical relevance. Eur J Clin Pharmacol 42, 313–317 (1992). https://doi.org/10.1007/BF00266354
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00266354