Development, Validation, and Application of the LC-MS/MS Method for Determination of 4-Acetamidobenzoic Acid in Pharmacokinetic Pilot Studies in Pigs.

Each drug has pharmacokinetics that must be defined for the substance to be used in humans and animals. Currently, one of the basic analytical tools for pharmacokinetics studies is high-performance liquid chromatography coupled with mass spectrometry. For this analytical method to be fully reliable, it must be properly validated. Therefore, the aims of this study were to develop and validate a novel analytical method for 4-acetamidobenzoic acid, a component of the antiviral and immunostimulatory drug Inosine Pranobex, and to apply the method in the first pharmacokinetics study of 4-acetamidobenzoic acid in pigs after oral administration. Inosine Pranobex was administered under farm conditions to pigs via drinking water 2 h after morning feeding at doses of 20, 40, and 80 mg/kg. For sample preparation, we used liquid-liquid extraction with only one step-protein precipitation with 1 mL of acetonitrile. As an internal standard, we used deuterium labeled 4-acetamidobenzoic acid. The results indicate that the described method is replicable, linear (r2 ≥ 0.99), precise (2.11% to 13.81%), accurate (89% to 98.57%), selective, and sensitive (limit of quantitation = 10 ng/mL). As sample preparation requires only one step, the method is simple, effective, cheap, and rapid. The results of the pilot pharmacokinetics study indicate that the compound is quickly eliminated (elimination half-life from 0.85 to 1.42 h) and rapidly absorbed (absorption half-life from 0.36 to 2.57 h), and that its absorption increases exponentially as the dose is increased.

Inosiplex affects the spectra of proton magnetic resonance spectroscopy in subacute sclerosing panencephalitis.

In vivo magnetic resonance techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have been some of the most useful tools for evaluation of neurologic diseases. In subacute sclerosing panencephalitis, magnetic resonance spectroscopy can be an additional tool for evaluation of disease progression or the efficacy of the treatment, such as interferon or inosiplex, compared with MRI. Inosiplex is one of the effective drugs for subacute sclerosing panencephalitis, but our in vivo and in vitro magnetic resonance spectroscopic study indicated that inosiplex affects the spectra, suggesting a possible failure of neurologic evaluation in a patient with subacute sclerosing panencephalitis treated with inosiplex.

Pharmacokinetics of zidovudine and concomitant inosine-pranobex in AIDS patients.

3'-azido-3'-deoxythymidine (AZT) was administered orally to 8 AIDS patients at a dose of 100 mg every 6 hours for 14 days. On days 8 - 14 the patients were also given 1 g inosine-pranobex (INPX) every 6 hours. On day 7, while the subjects were taking AZT alone and on day 14 while they were receiving AZT + INPX, blood samples were obtained over a 6-hour dosing interval for measurement of AZT by a specific AZT radioimmunoassay. AZT levels on day 14 were significantly higher than the corresponding levels on day 7, resulting in a 2-fold increase of the area under the serum concentration-time curve (AUC) and a prolongation of the mean half-life of AZT (44 to 70 min) during the INPX treatment. INPX is an immunomodulatory drug with an inhibitory effect on HIV. The potential advantages of a combined treatment AZT + INPX are: 1) need for lower dose of AZT for maintaining a therapeutic anti-retroviral level; 2) a longer interval period between AZT treatments; 3) a potential to enhance immunological response resulting from INPX treatment; 4) reduced costs of care for patients.