Factors Contributing to Variability in Drug Pharmacokinetics. Ii. Drug Distribution*

Abstract

Many factors determine the distribution of a drug within the body. All factors may be altered in physiological and pathological states, and this may result in a need to change either the dose of the drug administered or the dosage interval. Changes in plasma protein binding may also alter the interpretation of the relationship between total plasma drug concentration and drug effect, and in such circumstances the free drug concentration may provide a better guide to optimal therapy.

Pharmacokinetics of escalating single‐dose administration of cannabidiol to cats

“…For instance, the AUC after administration of a 2.5 mg/kg dose ranged from 8.1–165.9 ng/ml × h. This is about a 20‐fold difference between these individual cats. We suspect that as a lipid‐soluble drug, the fat content of each individual may serve as a reservoir for its uptake (Routledge, 1985 ). Given the large differences in body condition that we see across this population of cats, this may significantly affect its interindividual pharmacokinetic properties.…”

“…For instance, the AUC after administration of a 2.5 mg/kg dose ranged from 8.1-165.9 ng/ ml × h. This is about a 20-fold difference between these individual cats. We suspect that as a lipid-soluble drug, the fat content of each individual may serve as a reservoir for its uptake (Routledge, 1985).…”

A multi-route model of nicotine–cotinine pharmacokinetics, pharmacodynamics and brain nicotinic acetylcholine receptor binding in humans

“…The more recent utilization of PBPK models for evaluating the impact of human variability on internal dosimetry (Bois, 1999;Bois et al, 2010b;Marino et al, 2006;Nong et al, 2008;Yang et al, 2010) is of particular value for understanding nicotine pharmacokinetics; variability in metabolic and physiological parameters has been shown to contribute significantly to variability in drug and chemical dosimetry in blood and tissues (Bucher et al, 2011;Jack, 1985;Regardh, 1985;Routledge, 1985;Welling and Tse, 1984).…”