Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings
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...
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MDPI AG
2022-01-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/2/339 |
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| author | Guru R. Valicherla Roshan A. Katekar Shailesh Dadge Mohammed Riyazuddin Anees A. Syed Sandeep K. Singh Athar Husain Muhammad Wahajuddin Jiaur R. Gayen |
| author_facet | Guru R. Valicherla Roshan A. Katekar Shailesh Dadge Mohammed Riyazuddin Anees A. Syed Sandeep K. Singh Athar Husain Muhammad Wahajuddin Jiaur R. Gayen |
| author_sort | Guru R. Valicherla |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:52:05Z |
| format | Article |
| id | doaj.art-a9f35fbe670f4dcaac4e4772f67a0b4e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T00:52:05Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a9f35fbe670f4dcaac4e4772f67a0b4e2023-11-23T14:50:34ZengMDPI AGMolecules1420-30492022-01-0127233910.3390/molecules27020339Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo FindingsGuru R. Valicherla0Roshan A. Katekar1Shailesh Dadge2Mohammed Riyazuddin3Anees A. Syed4Sandeep K. Singh5Athar Husain6Muhammad Wahajuddin7Jiaur R. Gayen8Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, IndiaPSTi8 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.https://www.mdpi.com/1420-3049/27/2/339antidiabetic drugsPSTi8in vitro ADMEin vivo pharmacokineticsbioavailability |
| spellingShingle | Guru R. Valicherla Roshan A. Katekar Shailesh Dadge Mohammed Riyazuddin Anees A. Syed Sandeep K. Singh Athar Husain Muhammad Wahajuddin Jiaur R. Gayen Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings Molecules antidiabetic drugs PSTi8 in vitro ADME in vivo pharmacokinetics bioavailability |
| title | Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings |
| title_full | Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings |
| title_fullStr | Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings |
| title_full_unstemmed | Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings |
| title_short | Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings |
| title_sort | evaluation of the pharmacokinetics of the pancreastatin inhibitor psti8 peptide in rats integration of in vitro and in vivo findings |
| topic | antidiabetic drugs PSTi8 in vitro ADME in vivo pharmacokinetics bioavailability |
| url | https://www.mdpi.com/1420-3049/27/2/339 |
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