Update on the Pharmacokinetic Aspects of Antiretroviral Agents: Implications in Therapeutic Drug Monitoring

Abstract

The observed inter-individual variation in antiretroviral pharmacokinetics (PK) that results in a wide range of drug exposures from fixed-dose regimens has led to increasing interest in the clinical use of therapeutic drug monitoring (TDM) to individualize dosing of antiretroviral therapy (ART). The focus of this review is to provide an overview of literature available to support therapeutic drug monitoring among the current classes of antiretrovirals, suggest patient populations that may benefit from TDM and bring forth some of the limitations that may exist for widespread use of TDM in a traditional clinical setting.

Plasma protein binding: From discovery to development

“…Clinical dosages of ritonavir is adjusted, taking into consideration its 90% protein binding 42. It is highly recommended to account for plasma protein‐adjusted potencies for HIV drugs for their therapeutic efficacy43,44—in calculating inhibitory quotients (IQ) of ARV drugs, it is strongly suggested to correlate plasma trough unbound drug levels to the measure of susceptibility of HIV strain to the particular drug.…”

Factors Associated with Altered Pharmacokinetics in Substance Users and Non‐Substance Users Receiving Lopinavir and Atazanavir

“…Among all patients receiving ATV at study entry, only one was receiving a gastric acid‐lowering agent, which was a co‐formulation of famotidine, magnesium hydroxide, and calcium carbonate. Of note, this patient's ATV trough concentration was 0.593 µg/mL, which is above the minimum trough concentration required to suppress wild‐type virus 38 …”

Pharmacogenomics and the Toxicology Laboratory

“…There is evidence for the clinical benefi ts of therapeutic drug monitoring of nelfi navir, indinavir, ritonavir, amprenavir, saquinavir, lopinavir, efavirenz, delavirdine, zidovudine, and nevirapine (46) . To circumvent that problem, therapeutic drug monitoring of certain antiretrovirals, especially protease inhibitors, to individualize dose regimens of antiretrovirals has been strongly recommended in patients with acquired immunodefi ciency syndrome.…”