Presentation on theme: "Nutritional Influence of Drug Metabolism Kim Dalhoff Klinisk farmakologisk afdeling Rigshospitalet DIRAC kursus 4b Torsdag den 31. marts 2005 Food-Drug."— Presentation transcript:
Nutritional Influence of Drug Metabolism Kim Dalhoff Klinisk farmakologisk afdeling Rigshospitalet DIRAC kursus 4b Torsdag den 31. marts 2005 Food-Drug Interactions
Food-Drug Interactions Characteristics of the drug –Physical, chemical... Characteristics of the meal –Size, composition… Fasting (definition) No food intake for at least 1 hour before and at least 2 hours after drug intake
Food-Drug Interactions Clinical effect parameters Depending on the type of drug –E.g. antibacterial, antihypertensive, lipid lowering, anticoagulant...
Food-Drug Interactions Clinical relevance Dietary recommendations Proposed mechanism of interaction Consequences and qualifications of interaction Level/grade of evidence Schmidt & Dalhoff. Drugs 2002; 62:1481
Food-Drug Interactions Bisfosfonater ATC M05B Indikationsområde Hyperkalcæmi. Osteolytiske knoglemetastaser. Myelomatose. Paget’s knoglesygdom. Kalcifikation efter columnafrakturer og total hoftealloplastik. Osteoporose. Pamidronat. Ibandronat. Clodronat. Etidronat. Alendronat. Risedronat. Pamidronat.
Food-Drug Interactions Bisfosfonates have an exceptionally high affinity for chelation with dietary divalent cations (Ca 2+, Fe 2+ ) Clodronic acid BIO 31 % (½ hr before a meal) Clodronic acid BIO 90 % (with a meal) Clodronic acid BIO 66 % (2 hrs after a meal)
Food-Drug Interactions The various hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have very different chemical and pharmacokinetic properties Lovastatin BIO 50 % (with a regular meal) Lovastatin BIO (ingestion of fibres or fruit) Pravastatin BIO 31 % (with a regular meal)* Atorvastatin BIO (w a r m) Fluvastatin BIO (w a r m)
Food-Drug Interactions Conclusion Some drugs lead to BIO in the fed state and a risk of treatment failure (tetracycline, indinavir, bisfosfonates…) A lot of drugs lead to BIO in the fed state, but no major changes in clinical effect (pravastatin, phenoxymethylpenicillin, furosamide…) Some drugs lead to BIO in the fed state and increased drug effect. Usually desirable but may be a risk of toxicity (albendazole, griseofulvin, saquinavir, halofantrine*…)
Food-Drug Interactions Conclusion Other factors… Dietary habits Specific diseases Polyfarmaci Compliance Enzyme constitution
Grapefruit juice - Drug Interactions DG Bailey et al. Interactions of citrus juices with felodipine and nifedipine. Lancet 1991; 337: 268 M of A: Selective down-regulation of CYP3A4 in the small intestine Nifedipine. Felodipine. Nisoldipine. Nitrendipine. Triazolam. Midazolam. Terfenadine. Cyclosporine.
200 ml double-strength grapefruit juice 3 times daily for 2 days
Lovastatin BIO 1400 % Atorvastatin BIO 200 % Simvastatin BIO 1500 % Pravastatin BIO * Fluvastatin BIO * Grapefruit juice - Drug Interactions Lipid lowering agents
Almost complete presystemic meta- bolism by CYP3A4 The parent compound has arrhytmo- genic properties (prolongation of QTc interval) The drug was removed from the US market after a sudden unexpected death of a 29-year old healthy man ascribed to a drug - grapefruit juice interaction Grapefruit juice - Drug Interactions Terfenadine (antihistamine)
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