Presentation is loading. Please wait.

Presentation is loading. Please wait.

Nutritional Influence of Drug Metabolism Kim Dalhoff Klinisk farmakologisk afdeling Rigshospitalet DIRAC kursus 4b Torsdag den 31. marts 2005 Food-Drug.

Similar presentations


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:

1 Nutritional Influence of Drug Metabolism Kim Dalhoff Klinisk farmakologisk afdeling Rigshospitalet DIRAC kursus 4b Torsdag den 31. marts 2005 Food-Drug Interactions

2

3 Therapeutic failure Increased toxicity Pharmacokinetic interactions Pharmacodynamic interactions

4 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

5

6

7 Food-Drug Interactions Pharmacokinetic effect parameters Bioavailability = Effect –Absorption –First-pass metabolism

8

9 Food-Drug Interactions Clinical effect parameters Depending on the type of drug –E.g. antibacterial, antihypertensive, lipid lowering, anticoagulant...

10 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

11 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.

12 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)

13

14

15 Food-Drug Interactions Other bisfosfonates… Alendronic acid BIO  % (+/- 2 hrs of a meal) Etidronic acid BIO  100 % (with a meal)

16

17 Food-Drug Interactions Lipidsænkende midler (statiner) ATC C10A Indikationsområde Ren hypercholesterolæmi samt kombineret hyperlipidæmi Atorvastatin. Fluvastatin. Lovastatin. Pravastatin. Rosuvastatin. Simvastatin

18 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)

19

20 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*…)

21 Food-Drug Interactions Conclusion Other factors… Dietary habits Specific diseases Polyfarmaci Compliance Enzyme constitution

22 Food-Drug Interactions Conclusion Narrow therapeutic index Dose titration (TDM) –Hydralazine, tacrolimus, carbamazepine...

23 De vigtigste…

24

25 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.

26

27 200 ml double-strength grapefruit juice 3 times daily for 2 days

28 Lovastatin BIO  1400 % Atorvastatin BIO  200 % Simvastatin BIO  1500 % Pravastatin BIO  * Fluvastatin BIO  * Grapefruit juice - Drug Interactions Lipid lowering agents

29 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)

30

31

32

33


Download ppt "Nutritional Influence of Drug Metabolism Kim Dalhoff Klinisk farmakologisk afdeling Rigshospitalet DIRAC kursus 4b Torsdag den 31. marts 2005 Food-Drug."

Similar presentations


Ads by Google