Abstract
Aim: To study the preclinical pharmacokinetics of 4-hydroxy isoleucine (4-HIL) targeted for polycystic ovary syndrome. Methodology: The quantitative bioanalysis of 4-HIL in different biological matrices in female Sprage-Dawley rats using LC–MS/MS. Results: At 50 mg/kg, 4-HIL had 56.8% absolute oral bioavailability. It was quickly absorbed and distributed in various tissues in order of small intestine > kidney > ovary > spleen > lung > liver > heart > brain after oral administration. Moreover, 11.07% of 4-HIL was recovered in urine and feces within 72 h. Conclusion: 4-HIL levels in vital organs were found safe, as per tissue distribution results. Hence, 4-HIL could be used as promising therapeutics for management of polycystic ovary syndrome.
Graphical abstract
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.4155/bio-2023-0074
Acknowledgments
The authors thank the director of CSIR-Central Drug Research Institute, Lucknow for providing all facilities. The authors S Agrawal, SN Sanap, AC Bisen and A Biswas thank the Indian Council of Medical Research (New Delhi, India) for providing a Senior Research Fellowship assistance. The authors express their sincere thanks to Mr Deepak Sharma (Technical Officer, CSIR – Central Drug Research Institute) for his ongoing assistance throughout the work. The CSIR – Central Drug Research Institute, institutional communication no. is 10603.
Financial & competing interests disclosure
The authors has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved. The experiments were conducted according to applicable laws and institutional guidelines established by the Committee for the Purpose of Control and Supervision of Experiments on Animals, India (http://cpcsea.nic.in/Auth/index.aspx), and were authorized by the Institutional Animal Ethics Committee at Central Drug Research Institute (Lucknow, India; ref. no. IAEC/2022/67/Renew-0/Date-05/07/2022). Rats were kept at optimum conditions of laboratory-like regulated temperature (25 ± 2°C) and relative humidity (70 ± 2°C) and before an experiment, a 12/12-h dark/light cycle was maintained for 1 week.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2144/000112170