As a general rule, the maximal effect of enzyme induction is apparent in 7 to 10 days, although for drugs with a relatively long half-life, the full effect of induction may take even longer. The time to onset of induction is longer than the time to onset of inhibition and is based on the half-life of the inducing drug and the time required for new enzyme synthesis. Pharmacokinetic Inductionĭrugs that induce enzymes (inducers) cause an increase in the clearance of drugs metabolized by the same enzyme, leading to decreased concentrations of the other drug(s) ( Figure 3). Once the inhibitor is stopped, the effect of the inhibitor will typically dissipate after 3 to 5 half-lives. In the case of the cytochrome P-450 system of enzymes, inhibition of drug metabolism is usually rapid (based on drug half-life), with maximal effect occurring when the highest concentrations of the inhibiting drug are reached. Pharmacokinetic Inhibitionĭrugs that inhibit enzymes (inhibitors) cause a decrease in the metabolism of other drugs that depend on the same enzyme, leading to increased drug levels of medications and potential drug toxicity ( Figure 2). Some medications may act both as an inhibitor and as an inducer of a particular enzyme, which can further complicate drug interactions. Drug therapy may affect enzyme activity in one of three major ways: (1) by inhibiting the activity of the enzyme, (2) by inducing the activity of the enzyme, or (3) by acting as a substrate for the enzyme. The uridine diphosphate (UDP)-glucuronosyltransferase (UGT) 1A1 enzyme is an important mediator of pharmacokinetic interactions related to the metabolism of the integrase strand transfer inhibitors (INSTIs). Other enzymes in the cytochrome P-450 family, such as CYP1A2, 2C19, and 2D6, also play a key role. Overall, the CYP3A enzyme has the greatest impact on drug metabolism of antiretroviral medications this enzyme is abundant in both enterocytes of the small intestinal epithelium and hepatocytes ( Figure 1). There many cytochrome P-450 proteins, but the most important for drug metabolism belong to the CYP1, CYP2, or CYP3 families. Most clinically significant interactions are mediated by the cytochrome P-450 system, a superfamily of microsomal, catalytic enzymes responsible for the metabolism of more than half of all drugs. Pharmacokinetic interactions can occur between antiretroviral and concomitant medications during the absorption, metabolism, or elimination phases. This Topic Review will primarily focus on pharmacokinetic interactions that involve antiretroviral medications. Pharmacokinetic interactions generally have greater clinical relevance. Simplified, pharmacokinetics is what the body does to the medication, and pharmacodynamics is what the medication does to the body. In addition, genetic polymorphisms can influence the expression and availability of both receptor number and receptor affinity for a particular drug. Pharmacodynamics: Pharmacodynamics describes the relationship of a drug and its effect on the body’s receptors, which can be affected by the number and affinity of receptors, drug concentration, and genetics.Pharmacokinetic studies are used to define the steady-state concentration of a particular drug, taking into account dose, bioavailability, and clearance, as well as drug interactions that can alter the systemic concentration of coadministered medications. Pharmacokinetics: Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs in the body ( Table 1), which is often influenced by a variety of biological, physiological, and chemical factors within each patient.Drug interactions can be classified into one of two general categories: those that alter pharmacokinetics or those that alter pharmacodynamics. Understanding drug interactions is important for clinicians to provide effective and safe antiretroviral therapy. Pharmacokinetic and pharmacodynamics principles are fundamental to achieving the optimal response to antiretroviral drug therapy: successful antiretroviral therapy depends on attaining a therapeutic drug concentration that maximizes efficacy and minimizes toxicity. Phosphodiesterase Type 5 (PDE5) Inhibitors.Direct-Acting Oral Anticoagulant Medications.Oral Anticoagulants and Antiplatelet Therapy.Selective Serotonin Reuptake Inhibitors (SSRIs).Use of Corticosteroids Not Metabolized by CYP3A.Diuretics, ACE Inhibitors, and Angiotensin II Receptor Blockers.Resources for Drug Interactions Involving Antiretroviral Medications.Drug Interactions with Antiretroviral Medications.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |