Pharmacokinetic Interactions of Antihypertensive Drugs with Citrus Juices

It has been known that citrus juices cause pharmaceutical interactions with various kinds of medications. The citrus juice interactions are broadly divided into 2 types which are with increasing and decreasing of drug concentrations in plasma. That is, both types are categorized into pharmacokinetic interactions. In the "increasing" type interactions, grapefruit juice is the most important in the juices. Grapefruit juice makes an increase in the plasma drug concentrations due to the suppression of intestinal metabolization of the drugs. Since the danger of concomitant administration of drugs and grapefruit juice was discovered in 1989, drinking of the juice has been controlled in patients undergoing pharmaceutical therapies. The targeted medications for the restriction ranges from antilipemics to immunosuppressants. Antihypertensive drugs are one of the typical categories of drugs affected by such interaction. A feature of said drugs is that they are characterized as substrates of Cytochrome P-450 3A, the most important-drug metabolizing enzyme in the intestines. Dihydropyridine calcium channel antagonists, as well as verapamil in the antihypertensive drugs was representative of drug categories with such property. In this chapter, grapefruit juice interactions were described, and the latest knowledge presented, as a results of research utilizing statistical investigations with dihydropyridines. On the other hand, information about the "decreasing" type of interactions has been reported in a limited number of research results. Some clinical studies related to β-adrenergic-blocking agents (antihypertensives) such as celiprolol as well as fexofenadine (antihistamine), it was discovered that citrus juices such as orange juice and grapefruit juice reduce intestinal absorption of the drugs. In this chapter, results of the studies of the interactions are explained; and the research attributing an important ingredient in orange juice in the interaction with the β-blocker, is described.