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Abstract: FR-PO220

Preclinical Pharmacokinetics of a Novel Nicorandil Prodrug

Session Information

  • Pharmacology
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

  • 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

Authors

  • Gupta, Pramod, Unicycive Therapeutics Inc., Los Altos, California, United States
  • Khare, Atul, Unicycive Therapeutics Inc., Los Altos, California, United States
Background

Nicorandil, a potassium channel activator, is used to prevent or reduce angina. Limitations of nicorandil include serious gastrointestinal side effects and rapid absorption and elimination. A nicorandil prodrug may increase short half-life and improve safety profile of nicorandil. We present pharmacokinetic data in dogs for a novel nicorandil prodrug(UNI-494).

Methods

Groups of 3 beagle dogs were administered a single oral dose of 3, 10, or 30mg/kg UNI-494 at a volume of 5mL/kg. Clinical observations were recorded at approximately 1, 1.5, 2, 3, and 24h post-dose. Whole blood samples were collected pre-dose and 0.083, 0.25, 0.50, 1, 1.5, 2, 4, 8, and 24h post-dose to analyze systemic exposure to UNI-494and nicorandil. Dose and concentration parameters(Cmax and AUC) were used to generate linearity plots and calculate the coefficients of determination(r2) and slopes for UNI-494 and nicorandil.

Results

Mean Tmax, Cmax, and AUC of 3, 10, and 30mg/kg dose groups are displayed in Table 1. For the linearity plots, r2 values and slopes for dose vs. Cmax and dose vs. AUC are shown in Figures 1 and 2, respectively.

Conclusion

Nicorandil was rapidly formed from the prodrug UNI-494. Mean Cmax for nicorandil was >5-fold greater than that of UNI-494, demonstrating efficient conversion of the prodrug to active drug. The conversion was consistent across dose groups. These results indicate that UNI-494 is a rationally designed drug, and future studies should evaluate this promising treatment in the target population of patients with AKI.

Cmax, Tmax, and AUC by Dose Group and Analytes
Dose Group
(mg/kg)
AnalyteCmax
(ng/mL)
Tmax
(Hour)
AUC
(Hour*ng/mL)
3UNI-494430.334
Nicorandil1,3000.73,400
10UNI-4941780.3162
Nicorandil3,0701.511,400
30UNI-4941,5000.31,510
Nicorandil7,5301.338,000