In many patients, several drugs are given \nconcomitantly in order to increase the treatment efficiency or to treat \ndiseases occurring simultaneously. In such cases, pharmacokinetic \ninteractions between drugs may occur and the therapeutic efficacy or the\n toxicity of the drugs implied may be affected.\n<\/p>\n\n\n\n
Drug interactions may occur during absorption: a \ndrug can influence the rate or the extent of absorption of another drug.\n For example, metoclopramide hastens gastric emptying therefore \naccelerating the rate of absorption of certain drugs, e.g. paracetamol. \nCalcium forms insoluble complexes in the intestinal lumen with \ntetracycline, therefore decreasing its bioavailability. Erythromycin can\n dramatically increase the oral bioavailability of midazolam by \ninhibiting its hepatic first-pass effect. \n<\/p>\n\n\n\n
Distribution may also be influenced by drug \ninteractions. Most commonly, a drug that is highly bound to plasma or \ntissue proteins may be displaced from its binding sites by another drug.\n In an acute situation, this interaction may be significant if the \nconcentration of the displacer is sufficiently high to occupy most of \nthe protein binding sites. The sites available to bind the displaced \ndrug are thus lowered and the amount of unbound drug, the \npharmacologically active moiety, is increased. When the drug and the \ndisplacer are given chronically, the unbound concentration of the drug \ndepends on its extraction ratio. For drugs with a low extraction ratio, \nthere is an overall decrease in the total plasma concentration but no \nchange in the unbound concentration. On the other hand, for drugs with a\n high extraction ratio, the total plasma concentration is unchanged but \nthe unbound drug concentration is increased and this may lead to \ntoxicity.\n<\/p>\n\n\n\n
Most importantly, elimination may be affected by \ndrug interactions. A drug may inhibit the renal excretion of another \ndrug by competing with its renal tubular transport. Also, drug \nmetabolism may be strongly induced or inhibited<\/a>\n by the administration of a concomitant drug. The clearance of the drug \nis thus modified. Therefore, this type of interaction may easily lead to\n toxicity or ineffective therapy. Both induction and inhibition can \nmimic pharmacogenetic influences by phenocopying<\/a>.<\/p>\n\n\n\n