Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine

Vincent, John; Harris, Stuart; Foulds, George; Dogolo, Lisa C.; Willavize, Susan A.; Friedman, H.

doi:10.1046/j.1365-2125.2000.00283.x

Cited by 63 publications

(37 citation statements)

References 25 publications

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“…A milder but significant interaction has been detected with nitrendipine, pranidipine and nimodipine that exhibited bioavailability increments of 100, 73 and 50%, respectively (Soons et al, 1991;Fuhr et al, 1998;Hashimoto et al, 1998). However, little or no effect has been detected for nifedipine and amlodipine (Rashid et al, 1993;Josefsson et al, 1996;Vincent et al, 2000). These two dihydropyridines are characterized by a high bioavailability compared to felodipine, nisoldipine and nicardipine, which can explain the lack of the interaction.…”

Section: Amounts and Timingmentioning

confidence: 99%

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

2003

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More than a decade has passed since it was unintentionally discovered that grapefruit juice interacts with certain drugs. The coadministration of these drugs with grapefruit juice can markedly elevate drug bioavailability, and can alter pharmacokinetic and pharmacodynamic parameters of the drug. The predominant mechanism for this interaction is the inhibition of cytochrome P-450 3A4 in the small intestine, resulting in a significant reduction of drug presystemic metabolism. An additional mechanism is, presumably, the inhibition of P-glycoprotein, a transporter that carries drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug absorbed. Some calcium channel antagonists, benzodiazepines, HMG-CoA reductase inhibitors and cyclosporine are the most affected drugs. A single exposure to one glass of the juice can usually produce the maximal magnitude of the interaction. The data available so far, concerning this interaction and its clinical implications, are reviewed in this article. It is likely that more information regarding this interaction will accumulate in the future, and awareness of such is necessary for achieving optimal drug therapy.

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Section: Amounts and Timingmentioning

confidence: 99%

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

2003

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“…However, the pharmacokinetics of many other drugs was not altered by grapefruit juice. For example, grapefruit juice did not alter the bioavailability of digoxin, diltiazem, and amlodipine in human volunteers, and indinavir in HIV-positive patients (Becquemont et al, 2001;Sigusch et al, 1994;Vincent et al, 2000). Although these drugs undergo presystemic metabolism, CYP3A4 just contributes to a minor extent.…”

Section: Flavonoid -Drug Interactionsmentioning

confidence: 99%

Interactions of Herbs with Cytochrome P450

Zhou

Gao²,

Jiang

et al. 2003

Drug Metabolism Reviews

354

207

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A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb-drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products is complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb -drug metabolic interactions is difficult. However, herb-CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb -CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb-CYP interactions.Key Words: Herb; Cytochrome P450; Drug interactions.Abbreviations: Ah, aryl hydrocarbon; AUC, the area of the plasma concentrationtime curve; B[a]P, benzo[a]pyrene; C max , the maximum plasma concentration; CL int , intrinsic clearance; CYP, cytochrome P450; DAD, diallyl disulfide; DAS, diallyl sulfide; DASO, diallyl sulfoxide; DASO 2 , diallyl sulfone; DPS, dipropyl sulfide; DPDS, dipropyl disulfide; K i , inhibition constant; K m , Michaelis -Menten constant; NADPH, nicotinamide adenine dinucleotide phosphate; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; N-PiP, N-nitrosopiperidine; PgP, P-glycoprotein; PhIP...

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“…Drugs that have their serum concentrations increased by coadministration with grapefruit juice are listed in Table 7. [126][127][128][129][130][131][132] Patients should be advised to avoid taking medications on this list with grapefruit, unless advised to do so by their physician under controlled conditions.…”

Section: Drug-food Interactionsmentioning

confidence: 99%

Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know

Leather

2003

Bone Marrow Transplant

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Summary:Pharmacokinetic drug interactions among hematopoietic stem cell transplant recipients can result in either increases in serum concentrations of medications, which may lead to enhanced toxicity; or reduced serum concentrations, which can lead to treatment failure and the emergence of post transplant complications. The use of drugs that have a narrow therapeutic index, such as cyclosporine/tacrolimus (calcineurin inhibitors), increases the significance of these interactions when they occur. This report will review the clinical data evaluating the drug interactions of relevance to HSCT clinical practice, focusing on the pharmacokinetic interactions, and provides recommendations for managing these interactions to avoid both toxicity and treatment failure. Keywords: drug interactions; cytochrome P450; cyclosporine; tacrolimus; pharmacokinetic; CYP3A4; azoles A drug interaction is best defined as 'the possibility that one drug may alter the intensity of pharmacological effects of another drug that is given concurrently'. This results in either enhanced activity of the affected drug, which may lead to toxicity, or reduced activity of the affected drug, leading to therapeutic failure. It is also possible that there may be the appearance of a new effect that is not seen with either drug alone, for example, caspofungin and cyclosporine coadministration leading to elevated liver function tests. Drug interactions can be categorized as being either pharmacokinetic (PK) or pharmacodynamic in nature, and the remainder of this review will focus on PK interactions. Pharmacokinetic drug interactions -what are they?Pharmacokinetic drug interactions influence the disposition of the drug in the body. When drugs are ingested, they undergo several processes to produce an end effect, including absorption, distribution, metabolism, and excretion. Interactions between two or more drugs may affect any of these phases, including the modulation of hepatic drug biotransformation, renal clearance, altered distribution, or changes in plasma protein binding. The most clinically relevant mechanisms of PK drug interactions relate to metabolism and elimination of drugs from the body, and involve the cytochrome P450 (CYP) enzymes and the transporter P-glycoprotein at the hepatic and intestinal levels, and glomerular filtration and tubular secretion at the renal level. Cytochrome microsomal enzyme systemThe CYP microsomal enzyme system is a family of hemoproteins that is responsible for the oxidative biotransformation of endogenous substrates and xenobiotics. CYPs are expressed in several tissues, with the main drug metabolizing CYPs concentrated in the liver, with lower expression in the lungs, kidneys, intestines, and brain.1 Of the several different CYP isoforms identified, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 have the greatest involvement in drug metabolism. An extensive list of drugs metabolized by the various isoenzymes is outlined in Table 1. 2 The majority of oxidatively biotransformed drugs are metabolized, at least in part, ...

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Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine

Cited by 63 publications

References 25 publications

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance

Interactions of Herbs with Cytochrome P450

Drug interactions in the hematopoietic stem cell transplant (HSCT) recipient: what every transplanter needs to know

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