Introduction to pharmacokinetics: aminoglycosides in cystic fibrosis as a prototype

Pharmacokinetics is the study of the time course of drug absorption, distribution, metabolism, and excretion, allowing examination of the potential relationships between drug disposition and pharmacologic or toxicologic effects. The pharmacokinetics of the aminoglycosides and certain other drugs are different in patients with cystic fibrosis (CF), but this topic is controversial. Differences in disease severity between study subjects and in the methods used might explain the disparities. Understanding the fundamental principles of pharmacokinetics is necessary for the clinician to evaluate drug disposition data in patients with CF. To determine whether observed pharmacokinetic differences are attributable to CF, the investigator must consider a number of factors in the design and conduct of pharmacokinetic studies: analytical methods, study population selection, techniques for drug administration, method used to collect biologic specimens, evaluation of parallel rates and routes of drug excretion, and selection of pharmacokinetic and statistical techniques. Pharmacokinetic investigation in patients with CF should permit evaluation of the complete disposition profile for a drug, allow comparison between the experimental data and factors that characterize the disease state, and be rigorous enough to provide explanations for any observed variability in pharmacokinetics.