Pharmacometrics in Dose Finding or Dose Optimization of Anti-Retroviral and Anti-Tubercular Drugs

Sreedharan      Nair Sabarinath; Benjamin      Wu; Charles      Peloquin; Hartmut      Derendorf

Abstract

Drug development continues to be time consuming, expensive and less efficient, while drug therapy is often administered at suboptimal levels. This is particularly true with anti-infectives for HIV and tuberculosis. The application of pharmacometric principles and models to drug development and pharmacotherapy will improve the drug approval process and selection of optimal dosage regimens or therapeutic combinations. In this review we mainly focus on the utilities of pharmacometrics in the dose selections of anti-retroviral and anti-tubercular drugs. We will examine how pharmacometrics have been useful in the area of dose selections, preclinical to clinical scaling, subpopulation selections, combination therapies, adherence assessments, and resistance prevention dosing strategies.

Keywords: Pharmacokinetics, pharmacodynamics, pharmacometrics, anti-retroviral, anti-tubercular, modeling, simulation, Drug development, drug therapy, anti-infectives, tuberculosis, pharmacotherapy, therapeutic combinations, dose selections, adherence assessments