The Interplay between Pharmacokinetics and Pharmacodynamics.

Abstract

1. Tracy L. Sandritter, PharmD, BCPPS*,† 2. Matthew McLaughlin, MD, MS† 3. Michael Artman, MD‡ 4. Jennifer Lowry, MD† 1. *University of Missouri–Kansas City School of Pharmacy, Kansas City, MO 2. †Division of Clinical Pharmacology, Toxicology, and Therapeutic Innovation and 3. ‡Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO * Abbreviations: ADHD: : attention-deficit/hyperactivity disorder ADME: : absorption, distribution, metabolism, and elimination ADR: : adverse drug reaction CYP: : cytochrome P450 ED50: : pharmacologic effect in 50% of patients FDA: : Food and Drug Administration GFR: : glomerular filtration rate HLA: : human leukocyte antigen NSAID: : nonsteroidal anti-inflammatory drug OTC: : over the counter OTFC: : oral transmucosal fentanyl citrate P-gp: : P-glycoprotein SSRI: : selective serotonin reuptake inhibitor TD50: : toxic effect in 50% of patients TI: : therapeutic index Drug efficacy and safety depend on all aspects of pharmacokinetics and pharmacodynamics for optimal treatment. Assessment of efficacy, drug-drug interactions, and adverse drug reactions is essential for optimal outcomes. Pediatricians should fully consider these aspects of drug therapy every time a medication is prescribed. 1. Recognize that drug efficacy depends on multiple factors, including pharmacokinetics (absorption, distribution, metabolism, and elimination) and pharmacodynamics (the effect of the drug at the end organ). 2. Identify situations where dose adjustments are necessary to maintain the serum concentration within the normal therapeutic range and prevent toxicities. 3. Understand important intrinsic and extrinsic factors affecting drug response. 4. Review synergistic and detrimental drug-drug interactions that lead to altered pharmacodynamic responses due to the presence of another drug, a food, or herbal treatment. 5. Discuss predictable and idiosyncratic adverse drug reactions and identify federal adverse drug reporting systems. Pharmacokinetics and pharmacodynamics determine the clinical effects of drug therapy. Pharmacokinetics (what the body does to the drug) is defined as the quantitative study of drug absorption, distribution, metabolism, and elimination (ADME). Pharmacodynamics is clinically more elusive and difficult to precisely quantify. Pharmacodynamics is the study of the biochemical and physiological effects of drugs in the body. Thus, pharmacodynamics can be thought of as “what the drug does to the body.” Despite being 2 distinct entities, there is substantial interplay between pharmacokinetics and the resultant pharmacodynamics. Understanding this can be challenging. The correlation between the dose administered and the resulting drug concentration at the site of action ultimately contributes to the pharmacodynamic response. Thus, pharmacodynamics describes the relationship between drug concentration and the desirable clinical effects of a medication as well …