Pharmacokinetic and pharmacodynamic issues in the treatment of parasitic infections.
Despite increases in the incidence of many parasitic infections in recent years, the number of studies designed to improve the treatment of these infections has failed to keep pace with their huge impact on public health. Unfortunately, research and development in this field is not an economically attractive proposition for the pharmaceutical industry, and this neglect is exacerbated by the fact that many parasitic diseases have negligible profiles in countries that have the funds to research them. An absence of effective vaccines means that, for the foreseeable future, chemotherapy is likely to be the mainstay of disease management. This review describes the advances gained in our understanding of the relationship between pharmacokinetics and pharmacodynamics, with the aim of improving the way in which we use antiparasitic agents while at the same time highlighting those areas where there is an urgent need for further investigation. Unsurprisingly, much of our success has been in the chemotherapy of malaria, where the link between drug concentration and response is reasonably well characterised. For many other diseases, however, this link is poorly understood, in some cases because the mechanism of action of the drug has not been fully elucidated, or in other cases because a true pharmacodynamic endpoint may be unavailable. Overcoming these problems is critical if the clinician is to have the information necessary to enable optimal treatment of patients who may be severely ill and in need of immediate, life-saving attention.
Edwards
G
G
Department of Pharmacology and Therapeutics, The University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK. edwardsg@liv.ac.uk
Krishna
S
S
D000284:Administration, Oral; D000977:Antiparasitic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D010272:Parasitic Diseases / Q000188:drug therapy* / Q000469:parasitology; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D000977:Antiparasitic Agents