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Review
. 2023 Jan 1;24(1):746.
doi: 10.3390/ijms24010746.

Clinical Pharmacokinetics of Approved RNA Therapeutics

Seong Jun Jo  1 , Soon Uk Chae  1 , Chae Bin Lee  1 , Soo Kyung Bae  1
Affiliations
Review

Clinical Pharmacokinetics of Approved RNA Therapeutics

Seong Jun Jo et al. Int J Mol Sci. .

Abstract

RNA-mediated drugs are a rapidly growing class of therapeutics. Over the last five years, the list of FDA-approved RNA therapeutics has expanded owing to their unique targets and prolonged pharmacological effects. Their absorption, distribution, metabolism, and excretion (ADME) have important clinical im-plications, but their pharmacokinetic properties have not been fully understood. Most RNA therapeutics have structural modifications to prevent rapid elimination from the plasma and are administered intravenously or subcutaneously, with some exceptions, for effective distribution to target organs. Distribution of drugs into tissues depends on the addition of a moiety that can be transported to the target and RNA therapeutics show a low volume of distribution because of their molecular size and negatively-charged backbone. Nucleases metabolize RNA therapeutics to a shortened chain, but their metabolic ratio is relatively low. Therefore, most RNA therapeutics are excreted in their intact form. This review covers not only ADME features but also clinical pharmacology data of the RNA therapeutics such as drug-drug interaction or population pharmacokinetic analyses. As the market of RNA therapeutics is expected to rapidly expand, comprehensive knowledge will contribute to interpreting and evaluating the pharmacological properties.

Keywords: FDA-approved RNA therapeutics; absorption; distribution; excretion; metabolism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Years in which RNA therapeutics gained FDA approval. Eight antisense oligonucleotide drugs (blue), five single interfering RNA drugs (red), two mRNA drugs (orange), one aptamer drug (purple), and a mixture of single-stranded oligonucleotide drugs (green) were approved.
Figure 2
Figure 2
Common chemical structures of RNA therapeutics.
See this image and copyright information in PMC

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