| Abstract | Interakcija je međudjelovanje koje nastaje kada se sfere aktivnosti nekih supstancija preklapaju, na način da će djelovanje jedne supstancije utjecati na ponašanje druge. Farmakokinetska interakcija najčešći je tip interakcije kod istodobne primjene određenih sokova i lijekova, a nastaje kada jedna ili više supstancija iz soka mijenja apsorpciju, distribuciju, metabolizam i/ili ekskreciju lijeka. Glavnu skupinu enzima zaslužnih za metabolizam ksenobiotika čine enzimi iz porodice citokrom P450 (CYP), a u klinički značajnim interakcijama najčešće sudjeluju CYP1A2, 2C9, 2C19, 2D6, 2E1 i 3A4. Ako dođe do inhibicije citokroma, povećat će se koncentracija lijeka supstrata. Ako se radi o prolijeku, njegov smanjeni metabolizam smanjit će stvaranje aktivne molekule i farmakološko djelovanje. Osim CYP enzima, u interakcijama lijekova i sokova često sudjeluju i transporteri poput P-glikoproteina (P-gp) i organskog anionskog transportnog peptida (OATP). Voćni sok je najčešće konzumiran proizvod od voća zahvaljujući svojim nutritivnim i biološkim karakteristikama koje mogu zadovoljiti potrebe organizma te pružiti odgovarajuće pozitivne učinke po zdravlje. Voćni sokovi se prema fizikalnim svojstvima i tehnološkim procesima dobivanja mogu podijeliti u bistre, mutne i kašaste. Proizvodnja bistrih sokova temelji se na procesima koji pomažu uklanjanje netopljivih čestica koje uzrokuju mutnoću. Kod proizvodnje mutnih i kašastih sokova cilj je smanjiti taloženje netopljivih čestica te postići stabilizaciju i homogenost. Biološki aktivni spojevi (BAS) prirodni su nenutritivni sastojci hrane s pozitivnim učincima na ljudsko zdravlje. Flavonoidi su najrasprostranjenija skupina biljnih polifenola, a u voću su najzastupljeniji flavoni, flavonoli, flavanoli, flavanoni, antocijani i izoflavoni. U ovom radu obrađene su interakcije lijekova s voćnim sokovima od: grejpa, naranče, seviljske naranče, mandarine, klementine, pomela, limuna, limete, jabuke, brusnice, šipka, ananasa, borovnice, grožđa, banane, šljive, suhe šljive, manga, guave i avokada. Od lijekova u interakcije sa sokovima najčešće stupaju supstrati CYP3A4 (najzastupljenijeg enzima u metabolizmu ksenobiotika), npr. blokatori kalcijevih kanala, sildenafil, ciklosporin, statini, karbamazepin itd., a neki od polifenola inhibitora CYP3A4 iz voća su: bergamotin i 6', 7'-dihidroksibergamotin iz grejpa, seviljske naranče i pomela; flavonoli, antocijani i fenolne kiseline iz brusnica; naringin i naringenin iz pomela; kvercetin, kemferol i galna kiselina iz šipka te resveratrol iz grožđa. |
| Abstract (english) | Interaction occurs when spheres of activity of multiple substances overlap in a way that the effect of one substance will influence the behaviour of another. In most cases of interactions between drugs and fruit juices the interaction is of pharmacokinetic nature, meaning that one or more substance from the juice modifies the absorption, distribution, metabolism and/or excretion of the drug. The cytochrome P450 (CYP) group of enzymes is responsible for the metabolism of most xenobiotics, and the ones most involved in drug interactions are CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. When cytochrome inhibition occurs, the concentration of the drug substrate rises. On the contrary, if the substrate is a prodrug, the concentration of its active metabolite and therapeutic effect will reduce. Besides the CYP enzymes, transporters such as P-glycoprotein (P-gp) and organic anion transporter peptide (OATP) often participate in drug-fruit juice interactions. Fruit juice is the most popular fruit product thanks to its nutritious and health-promoting properties. Considering its physical properties and manufacturing processes, fruit juices can be divided into clear, cloudy and puree. The manufacture of clear juice is based on processes that help remove insoluble particles that disenable juice transparency. The goal of cloudy and puree juice production is to prevent sedimentation of insoluble particles and achieve stability and homogeneity. Biologically active substances are naturally present and non-nutritional food ingredients that have a benficial effect on one's health. Flavonoids are the most widespread group of plant polyphenols, the most common in fruits being flavones, flavonols, flavanones, flavanols, anthocyanins and isoflavones. The fruit juices responsible for interacting with drugs covered in this thesis where made from: grapefruit, orange, Seville orange, tangerine, clementine, pomelo, lemon, lime, apple, cranberry, pomegranate, pineapple, blueberry, grape, banana, plum, prune, mango, guava and avocado. Drugs that are most frequently involved in interactions with juices are substrates of CYP3A4 (the most common xenobiotic metabolising enzyme), namely calcium channel blockers, sildenafil, cyclosporine, statins, carbamazepine etc., and most notable fruit juice polyphenols that inhibit CYP3A4 are: bergamottin and 6', 7'-dihydroxybergamottin from grapefruit, Seville orange and pomelo; flavonols, anthocyanins and phenolic acids from cranberry; naringin and naringenin from pomelo; quercetin, kaempherol and gallic acid from pomegranate and finally resveratrol from grape. |
