Drug Interactions and Clinical Pharmacokinetics

Abstract

Some drugs influence the gastro-intestinal absorption, distribution , metabolism or renal excretion of other drugs, i.e., processes involved in pharmacokinetic interactions. The clinical consequences of pharmacokinetic drug-drug interactions will be either an increase or a decrease in known therapeutic or toxic effects of the interacting drug. In order to evaluate the importance of drug interaction affecting gastro-intestinal absorption, it is necessary to distinguish between interactions which alter the rate of absorption of another drug and those which alter the amount of drug absorbed. Many drugs displace other drugs from their protein binding sites in vitro. This may cause an increase in the pharmacological effect of the displaced drug. However, much discrepancy exists between in vitro findings. In some cases, the enhanced effect only seems to be a temporary phenomenon. The degree of protein binding and the size of apparent volume of distribution (Vd) must also be taken into consideration. Perhaps the importance of interaction involving protein binding has been overemphasized. Barbiturates, glutethimide, rifampicin and phenytoin increase the rate of drug metabolism in man. The most important interactions reported are between oral anti-coagulants and barbiturates. After withdrawal of these hepatic microsomal enzyme inducing drugs, it takes 2 to 3 weeks before the rate of drug metabolism reaches the pretreatment level. In this period, risk of haemorrhage exists. Induction seems to be dose-dependent, but not all persons are inducible. Many drugs compete for the drug metabolising enzyme system in the liver and consequently some drugs inhibit the biotransformation of other drugs. The time course of these interactions depends on the pharmacokinetic properties of the drug involved, and these interactions also seem to be dose-dependent. The most important of such interactions, clinically involved the oral sulphonylurea hypoglycaemic drugs and the antiepilepic drug phenytoin. Drugs are eliminated by urinary excretion through three mechanisms: glomerular filtration, tubular reabsorption, and active tubular secretion. The most important interactions seem to be those involving competition for tubular secretion.

Review article: drug interactions with agents used to treat acid‐related diseases

“…Drug–drug interactions may also result from changes in distribution. Drugs may compete for binding sites on plasma proteins, and displacement interactions may markedly increase free drug levels and thus pharmacological effects 10 . 11 Phase II reactions (conjugation with acids) can also be a significant source of drug–drug interactions because prescription drugs or other agents can induce or inhibit the enzymes involved in these processes 12 .…”

“… 11 Phase II reactions (conjugation with acids) can also be a significant source of drug–drug interactions because prescription drugs or other agents can induce or inhibit the enzymes involved in these processes 12 . 13 Pharmacological interference with renal elimination by drugs that affect glomerular filtration, tubular reabsorption, or tubular secretion may also cause interactions between coadministered drugs 10 …”

Studies of Interactions of Valsartan, Glimepiride and Ciprofloxacin HCl by DSC and HPLC

“…However, interactions may also exist between drugs and foods (drug-food interactions). These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances (National Prescribing Service, 2009;Kristensen, 1976). Patients with diseases like kidney/heart transplantation or failure, diabetes mellitus and hypertension, anemia, bone and lipid disorders and so on are frequently prescribed numerous medications.…”

In vitro Interaction of Metformin with Diclofenac in Aqueous Medium

“…The area of drug interaction involves and correlates all the disciplines of drug management and health care system relevant to the contemporary practice of medicine. [1][2][3] Knowledge of drug interaction may allow early recognition and prevention of adverse consequences. The most comprehensive understanding of clinically significant drug interaction can be achieved by combining knowledge of the mechanism of drug interaction with recognition of the high-risk patients and the identification of drug with a narrow therapeutic index.…”