Question

what is antiretroviral   pharmacodynamics and Antifungal pharmacodynamics.

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Answer 1

Antiretroviral Pharmacodynamics

The identification of drug targets against the human immunodeficiency virus has led to the development and approval of several antiretroviral agents. Drug monotherapy and non-adherence to prescribed regimen have led to the emergence of drug resistance and current drug regimens consisting of at least three drugs are recommended. The relationship between drug exposure or concentrations and response has been described for most agents, both as single agents and in combination with other drugs. The introduction of fixed-dose formulation and the fact that new drugs are only tested in combination with other antiretrovirals introduces issues in determining the exact pharmacodynamics of single agents. However, favorable responses such as viral suppression, now defined as HIV-1 RNA level <20–50 copies/mL, and restoration of immune function as evidenced by increased CD4+ cell counts, remain the benchmark in efficacy comparison. Further, HIV-RNA levels, CD4+ cell counts, and resistance-associated mutations at baseline often predict virological failure or success of HIV drugs. Although therapeutic drug monitoring may have advantages in specific populations, it is not indicated for routine use and has limited utility for some drug classes such as nucleoside

Antifungal pharmacodynamics

The treatment of invasive fungal diseases constitutes a significant unmet medical need. There are relatively few antifungal agents in clinical development and a paucity of novel targets. Morbidity and mortality remain high and clinical outcomes are compromised by submaximal efficacy, emergence of drug resistance and drug-related toxicity. Thus, new antifungal agents are urgently required. A deep understanding of exposure–response relationships underpins the development of safe and effective clinical regimens of any therapeutic agent. Pharmacokinetics (PK) and pharmacodynamics (PD) is increasingly recognized as a vital tool in the development of new antimicrobial agents and maximizes the probability that the right dose will be studied the first time. There is currently no information or agreement as to what constitutes an adequate PK/PD package for the development of a new antifungal agent. This review provides a summary of the achievements of antifungal PK/PD for the treatment of invasive candidiasis, invasive aspergillosis and cryptococcal meningoencephalitis, and outlines the necessary components of a PK/PD package for a new antifungal agent. Such information is critical for the accelerated and efficient development of new agents and enables improved clinical outcomes to be secured.