Bioavailability and dose proportionality of a highly lipophilic phenolic antioxidant
Creators: name: Yanovskaya, Elena A.
name: Frelikh, Galina A.
name: Lakeev, Alexander P.
name: Smolyakova, Vera I.
name: Chernysheva, Galina A.
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Biochemistry
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Cancer
subject: Virology
subject: Cardiology

description: IBP (2,6-diisobornyl-4-methylphenol) is a camphene derivative with unique pharmacological properties and low toxicity. It exhibits pronounced antioxidant and membrane-protective effects, making it a promising cardio- and neuroprotector.The aim of the study was investigating the pharmacokinetics of IBP in rats after intravenous (1 mg/kg) and oral administration at three doses (10, 25, 50 mg/kg). Specifically, we focused on assessing the bioavailability and dose proportionality following oral administration.Blood samples were collected <i>via</i> a jugular vein catheter, and plasma samples were analysed using a validated HPLC-MS/MS method. The calculation of pharmacokinetic parameters was performed by both non-compartmental and compartmental approaches. The proposed dosage form for intravenous administration was a multicomponent mixture containing <i>N</i>-methyl-2-pyrrolidone.Concentration of IBP in the body after intravenous administration decreased over time, exhibiting bi-exponential decay kinetics. IBP reached peak concentrations immediately and was rapidly distributed into the peripheral compartment after intravenous administration. The systemic exposure after oral administration was proportional to the dose. The calculated absolute oral bioavailability of IBP was no more than 20%.The value of the average half-life of IBP after intravenous administration exceeded similar values after oral administration by 1.5–1.6 times. IBP (2,6-diisobornyl-4-methylphenol) is a camphene derivative with unique pharmacological properties and low toxicity. It exhibits pronounced antioxidant and membrane-protective effects, making it a promising cardio- and neuroprotector. The aim of the study was investigating the pharmacokinetics of IBP in rats after intravenous (1 mg/kg) and oral administration at three doses (10, 25, 50 mg/kg). Specifically, we focused on assessing the bioavailability and dose proportionality following oral administration. Blood samples were collected <i>via</i> a jugular vein catheter, and plasma samples were analysed using a validated HPLC-MS/MS method. The calculation of pharmacokinetic parameters was performed by both non-compartmental and compartmental approaches. The proposed dosage form for intravenous administration was a multicomponent mixture containing <i>N</i>-methyl-2-pyrrolidone. Concentration of IBP in the body after intravenous administration decreased over time, exhibiting bi-exponential decay kinetics. IBP reached peak concentrations immediately and was rapidly distributed into the peripheral compartment after intravenous administration. The systemic exposure after oral administration was proportional to the dose. The calculated absolute oral bioavailability of IBP was no more than 20%. The value of the average half-life of IBP after intravenous administration exceeded similar values after oral administration by 1.5–1.6 times.