Pharmacokinetic Aspects of Antifungal Therapy

Abstract

The pharmacokinetic study of drugs, analysis of the time course of a drug substance in the body, is no longer novel in clinical therapeutics. The application of the concepts of pharmacokinetics to the discovery and development of better therapeutic agents, particularly within the pharmaceutical industry, is growing rapidly. There are several aspects of this process which are particularly important in the development of antimicrobial agents. Thus, for example, drug discovery projects are now focussing on the need to achieve high systemic availability following oral administration; the potential benefit in targeting drugs to particular tissues such as the CNS or via specific routes of elimination such as in urine or body secretions to treat topical infections; and the need to obtain drugs with a sufficiently long duration of action to achieve once daily dosing. In addition, the relationship between the in vitro potency of drugs in primary screens and their efficacy in vivo is often poorly understood, and discovery project scientists often cannot rationalise the efficacy of their novel compounds in vivo without an awareness of their pharmacokinetics. Consequently, both the practising clinician and the project scientist need to have an understanding of what impact the pharmacokinetic profile of the drugs they propose for antifungal therapy will have on their efficacy.