Biopharmaceutics, pharmacokinetics and pharmacodynamics of antituberculosis drugs.
Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB as well as the emergence of resistance resulted in an unforeseen increase in the number of TB cases, including multi-drug resistant (MDR) and extensively-drug resistant (XDR) forms of TB. Consequently, there is an urgent need to develop novel, fast acting antituberculosis drugs with high potency that can provide treatment options for all forms of TB. It is well known that the current TB drugs exhibit differences in their in vivo activity profile and these differences are largely determined by their pharmacodynamics (PD), i.e. intrinsic antibacterial activity, biopharmaceutical properties such as solubility and permeability, and pharmacokinetic (PK) properties such as drug exposure, tissue distribution, and protein binding. An understanding of the relationships among these properties is considered key for a rational use of antituberculosis therapeutics. The current review provides a comprehensive summary of physicochemical/biopharmaceutical, PK, and PD properties of currently used antituberculosis drugs and novel agents under development. Also, a brief review of PK/PD parameters of current TB drugs is given and properties of a desirable TB drug target and drug molecule are outlined. The information provided herewith may be useful in the optimization of biopharmaceutical and PK/PD characteristics in the development of novel TB therapeutics and in the design of optimal treatment regimens.
Budha
Nageshwar R
NR
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38162, USA.
Lee
Richard E
RE
Meibohm
Bernd
B
D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001702:Biopharmaceutics; D006801:Humans; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents