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1.
Bioanalysis ; 15(2): 83-98, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36916612

ABSTRACT

Background: Raspberry ketone (RK), derived from red raspberry fruit (Rubus idaeus, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC-MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10-5 cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.


Using LC­MS/MS, a method was developed and validated for RK, and investigated the preclinical pharmacokinetics and bioavailability in Sprague Dawley rats.


Subject(s)
Butanones , Tandem Mass Spectrometry , Rats , Animals , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Microsomes, Liver , Reproducibility of Results
2.
Molecules ; 27(2)2022 Jan 06.
Article in English | MEDLINE | ID: mdl-35056659

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.


Subject(s)
Blood Proteins/metabolism , Chromogranin A/antagonists & inhibitors , Microsomes, Liver/metabolism , Peptide Fragments/pharmacology , Peptide Fragments/pharmacokinetics , Animals , Biological Availability , Female , In Vitro Techniques , Male , Microsomes, Liver/drug effects , Protein Binding , Rats , Rats, Sprague-Dawley , Tissue Distribution
3.
Drug Dev Res ; 82(7): 927-944, 2021 11.
Article in English | MEDLINE | ID: mdl-33988872

ABSTRACT

Advancement in biotechnology provided a notable expansion of peptide and protein therapeutics, used as antigens, vaccines, hormones. It has a prodigious potential to treat a broad spectrum of diseases such as cancer, metabolic disorders, bone disorders, and so forth. Protein and peptide therapeutics are administered parenterally due to their poor bioavailability and stability, restricting their use. Hence, research focuses on the oral delivery of peptides and proteins for the ease of self-administration. In the present review, we first address the main obstacles in the oral delivery system in addition to approaches used to enhance the stability and bioavailability of peptide/protein. We describe the physiochemical parameters of the peptides and proteins influencing bioavailability in the systemic circulation. It encounters, many barriers affecting its stability, such as poor cellular membrane permeability at the GIT site, enzymatic degradation (various proteases), and first-pass hepatic metabolism. Then describe the current approaches to overcome the challenges mentioned above by the use of absorption enhancers or carriers, structural modification, formulation and advance technology.


Subject(s)
Drug Delivery Systems , Peptides , Administration, Oral , Biological Availability , Proteins
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