Abstract

4′-cyano-2′-deoxyinosine (SK14-061a), a novel nucleoside analog based on inosine, has antiviral activity against the human immunodeficiency virus type 1 that has the ability to acquire resistance against many types of reverse transcriptase inhibitors based on nucleosides. The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats. For this purpose, we first developed and validated an analytical method for quantitatively determining SK14-061a levels in biological samples by a UPLC system interfaced with a TOF-MS system. A rapid, simple and selective method for the quantification of SK14-061a in biological samples was established using liquid chromatography mass spectrometry (LC-MS) with solid phase extraction. The pharmacokinetic properties of SK14-061a in rats after oral administration were then evaluated using this LC-MS method. SK14-061a was found to be relatively highly bioavailable, is rapidly absorbed from the intestinal tract, and is then mainly distributed to the liver and then ultimately excreted via the urine in an unchanged form. Furthermore, the simultaneous administration of SK14-061a with the nucleoside analog, entecavir, led to a significant alteration in the pharmacokinetics of SK14-061a. These results suggest that the SK14-061a has favorable pharmacokinetic properties with a high bioavailability with the potential for use in oral pharmaceutical formulations, but drug-drug interactions should also be considered.

Highlights

  • Nucleoside/nucleotide-based compounds have been approved by the US Food and Drug Administration (FDA) and are widely used in the clinics for the treatment of various types of disorders, including hepatitis B, human immunodeficiency virus type 1 (HIV-1) and cancer

  • The absolute recovery results for SK14-061a in plasma were 92.4 ± 10.9%, indicating that this solid phase extraction (SPE) method has an acceptable extraction recovery. These results indicate that our established liquid chromatography mass spectrometry (LC-MS) conditions and the extraction method are adequate for the quantification of SK14-061a in biological samples

  • The present study reports on the first hard data regarding the pharmacokinetic properties of a novel anti-HIV agent, SK14-061a, after its oral administration in rats

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Summary

Objectives

The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats

Methods
Results
Conclusion
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