12 research outputs found

    Pharmacokinetic properties of a novel inosine analog, 4′-cyano-2′-deoxyinosine, after oral administration in rats

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    <div><p>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.</p></div

    Time course for the plasma concentration of SK14-061a after oral administration at a dose of 1 mg/kg in rats.

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    Venous blood samples were collected at 15 min, 45 min, 90 min, 3, 4.5, 6 and 9 hr after oral administration. The SK14-061a concentrations in plasma were measured by LC-MS combined with the SPE method. The values are the mean ± SD. (n = 4).</p

    (A) Time course for the plasma concentration of ETV after an oral administration of ETV alone (closed circle) or combination with SK14-061a (open circle) at doses of 1 mg/kg in rats. (B) Time course for the concentration of SK14-061a in plasma after the oral administration of SK14-061a alone (closed circle) or combination with ETV (open circle) at doses of 1 mg/kg in rats.

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    <p>Venous blood samples were collected at 15 min, 45 min, 90 min, 3, 6 and 9 hr after administration. The SK14-061a and ETV concentrations in plasma were measured using LC-MS with the SPE method. The data for SK14-061a alone are quoted from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0198636#pone.0198636.g003" target="_blank">Fig 3</a>. The values are the mean ± SD. (n = 4).</p

    LC-MS chromatograms of SK14-061a in urine.

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    <p>Urine samples were collected in a metabolic cage and were pretreated on an SPE column (Waters Oasis MCX 96 well plate) for extracting SK14-061a as described in the Materials and Methods section.</p
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