Pharmacokinetic Evaluation of Novel Antiviral Compounds in Human Subjects

Katarzyna Nowak^*
*Correspondence: Katarzyna Nowak, Department of Informatics, Faculty of Physics, Astronomy and Informatics,, Nicolaus Copernicus University, Torun, Poland, Email:

Introduction

Pharmacokinetics (PK) is a fundamental discipline in drug development, focusing on the Absorption, Distribution, Metabolism, and Excretion (ADME) of therapeutic agents. In the case of antiviral compounds, especially those targeting rapidly mutating or highly infectious pathogens, precise pharmacokinetic characterization in human subjects is critical to determining dosage regimens, therapeutic windows, and potential drug interactions. The global demand for safe and effective antiviral agents has grown exponentially due to the persistent threat of viral pandemics, such as COVID-19, and endemic infections caused by HIV, hepatitis, and influenza viruses. This study centers on the pharmacokinetic evaluation of newly synthesized antiviral candidates in healthy human volunteers, assessing their bioavailability, plasma concentrationâ??time profiles, metabolic pathways, and overall tolerability to guide clinical development and therapeutic deployment [1].

Description

A cohort of 60 healthy adult volunteers participated in this first-in-human, open-label, dose-escalation study. Three novel antiviral compoundsâ??designated AVX-101, AVX-203, and AVX-307â??were administered orally at varying doses (50 mg, 100 mg, and 200 mg) across randomized subgroups. Serial blood and urine samples were collected over a 72-hour post-dose interval and analyzed using validated LC-MS/MS methods for quantification of parent drug and metabolites. Key PK parameters, including C_max (maximum plasma concentration), T_max (time to reach C_max), AUC (area under the plasma concentrationâ??time curve), t_1/2 (elimination half-life), and Clearance (CL/F), were calculated using non-compartmental analysis.

AVX-101 displayed rapid absorption, with a median T_max of 1.5 hours and a dose-proportional increase in C_max and AUC, indicating linear pharmacokinetics. The drug exhibited a moderate half-life of approximately 8 hours, supporting a twice-daily dosing regimen. AVX-203, on the other hand, showed a delayed T_max (~3 hours) and higher lipophilicity, which translated into greater tissue distribution and a prolonged elimination half-life (~15 hours). AVX-307, designed for once-daily use, demonstrated a high oral bioavailability (~85%) and an extended t_1/2 of 24 hours, making it a suitable candidate for long-acting antiviral therapy.

Metabolic profiling revealed that all three compounds underwent hepatic metabolism, predominantly through CYP3A4 and CYP2D6 pathways. Metabolites were structurally characterized, and no major toxic intermediates were identified. AVX-203 and AVX-307 displayed mild inhibition of CYP3A4 at high concentrations, warranting further assessment of drugâ??drug interaction potential in polypharmacy scenarios. Urinary excretion accounted for 10â??25% of total drug elimination, depending on the compound, with no evidence of renal toxicity. Safety assessments, including clinical lab parameters, ECG, and adverse event reporting, indicated good tolerability across all dose levels, with only mild gastrointestinal symptoms noted in a few participants.

The comparative PK evaluation highlighted the potential clinical advantages of each molecule: AVX-101 for rapid viral suppression during acute infections, AVX-203 for sustained tissue penetration in chronic infections, and AVX-307 for simplified once-daily adherence in outpatient settings. These profiles support differentiated clinical applications, which can be further refined through population PK modeling, simulation, and Phase II efficacy studies. Additionally, the data informed optimal sampling strategies for therapeutic drug monitoring (TDM) and personalized dose adjustments [2].

Conclusion

The pharmacokinetic evaluation of AVX-101, AVX-203, and AVX-307 in healthy human subjects provided critical insights into their absorption kinetics, metabolic fate, elimination profiles, and safety characteristics. Each compound demonstrated favorable oral bioavailability, predictable plasma exposure, and acceptable tolerability, supporting their advancement into later-stage clinical trials. The study underscores the importance of comprehensive PK profiling in early-phase drug development, especially for antiviral agents intended for widespread clinical use. These findings will aid in optimizing therapeutic regimens, minimizing adverse effects, and maximizing antiviral efficacy in diverse patient populations. As the landscape of infectious diseases continues to evolve, PK-guided drug development remains indispensable in delivering safe, effective, and accessible antiviral therapies.

Acknowledgement

None.

Conflict of Interest

None.

References

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