Interaction is a familiar term to most biostatisticians. When the effect of one factor differs across levels of a second factor, interaction between the factors is present. Drug disposition refers to the processes of how a drug is absorbed, distributed, metabolized (broken down), and excreted [6]. Variations in drug disposition and/or effect may result from interactions with, for example, disea...

Recent analyses demonstrated that metabolites are unlikely to contribute significantly to clinical inhibition of cytochrome P450 (P450)-mediated drug metabolism, and that only ∼2% of this type of drug interaction could not be predicted from the parent drug alone. Due to generally increased polarity and decreased permeability, metabolites are less likely to interact with P450s, but their disposi...

Liver disease changes the disposition properties of drugs, complicating drug therapy management. We present normal and "diseased" versions of an abstract, agent-oriented In Silico Livers (ISLs), and validate their mechanisms against disposition data from perfused normal and diseased rat livers. Dynamic tracing features enabled spatiotemporal tracing of differences in dispositional events for di...

The clinical responses to drug administration can be greatly influenced both by the chronological age of the patient and by the relative maturity of the particular organ system that is being targeted. Human development follows a continuum of time-related events. There are unique therapeutic differences and concerns associated with the treatment of the very young and the elderly patient. Age-dep...

Physiological, hormonal, and genetic differences between males and females affect the prevalence, incidence, and severity of diseases and responses to therapy. Understanding these differences is important for designing safe and effective treatments. This paper summarizes sex differences that impact drug disposition and includes a general comparison of clinical pharmacology as it applies to men ...

Genetic polymorphisms of drug metabolizing enzymes are well recognized. This review presents molecular mechanisms, ontogeny and clinical implications of genetically determined intersubject variation in some of these enzymes. Included are the polymorphic enzymes N-acetyl transferase, cytochromes P4502D6 and 2C, which have been well described in humans. Information regarding other Phase I and Pha...

describing drug disposition in eye compartments to simulate disposition of clonidine after topical (eye drop) administration [1]. This example extends the methodology to describe the disposition of timolol in different eye tissues and plasma after topical administration. Timolol is a nonselective beta-adrenoceptor antagonist used to lower intraocular pressure (IOP) [2]. A serious disadvantage o...

During the last decade, the application of pharmacokinetic and pharmacodynamic modeling techniques has become an increasingly important aspect of contemporary clinical psychopharmacology (1–5). These techniques have been applied during the process of development of new drug entities as well as for the improved understanding of the clinical actions of drugs that are already marketed. Techniques ...