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. 2022 Jan 6;27(2):339.
doi: 10.3390/molecules27020339.

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

Guru R Valicherla  1   2 , Roshan A Katekar  1   2 , Shailesh Dadge  1 , Mohammed Riyazuddin  1 , Anees A Syed  1   2 , Sandeep K Singh  1   2 , Athar Husain  1   2 , Muhammad Wahajuddin  1   2 , Jiaur R Gayen  1   2   3
Affiliations

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings

Guru R Valicherla et al. Molecules. .

Abstract

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood-plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood-plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.

Keywords: PSTi8; antidiabetic drugs; bioavailability; in vitro ADME; in vivo pharmacokinetics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Stability of PSTi8 peptide in (A) rat plasma and (B) rat liver microsomes. Data are represented in n = 3 with a mean ± SD.
Figure 2
Figure 2
Pharmacokinetic studies of the PSTi8 peptide in different routes of administration in male SD rats. Plasma concentration against time profiles of the PSTi8 peptide at a dose of 5 mg/kg, after (A) i.v., (B) i.p. and (C) s.c. administration to each group. Data are represented in n = 6 with the mean ± SD.
Figure 3
Figure 3
Dose proportionality pharmacokinetic studies of the PSTi8 peptide in male SD rats. Plasma concentration against time profiles of PSTi8 peptide after i.p. administration at 10 and 20 mg/kg to each group. Data are represented in n = 6 with the mean ± SD.
Figure 4
Figure 4
Pharmacokinetic studies of the PSTi8 peptide in female SD rats. Plasma concentration against time profiles of the PSTi8 peptide after at a dose of 5 mg/kg (A) i.v. and (B) i.p. administration to each group. Data are represented in n = 6 with the mean ± SD.
See this image and copyright information in PMC

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