In vivo pharmacological evaluation of a lactose-conjugated luteinizing hormone releasing hormone analogue

International Journal of Pharmaceutics
Shayli Varasteh MoradiIstvan Toth

Abstract

In the current study, the efficacy and pharmacokinetic profile of lactose-conjugated luteinizing hormone releasing hormone (LHRH) was examined following oral administration in male rats. A rapid and sensitive liquid chromatography/mass spectrometry technique was developed and applied for measuring the concentration of lactose[Q(1)][w(6)]LHRH (compound 1) in rat plasma in order to allow measurement of pharmacokinetic parameters. LH release was evaluated using a sandwich ELISA. Maximum serum concentration (Cmax = 0.11 μg/ml) was reached at 2h (Tmax) following oral administration of the compound at 10mg/kg. The half-life was determined to be 2.6h. The absolute bioavailability of the orally administered compound was found to be 14%, which was a remarkable improvement compared to zero-to-low oral bioavailability of the native peptide. Compound 1 was effective in stimulating LH release at 20mg/kg after oral administration. The method was validated at a linear range of 0.01-20.0 μg/ml and a correlation coefficient of r(2) ≥ 0.999. The accuracy and precision values showed the reliability and reproducibility of the method for evaluation of the pharmacokinetic parameters. These findings showed that the lactose derivative of LHRH has a th...Continue Reading

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May 29, 2013·Bioorganic & Medicinal Chemistry·Shayli Varasteh MoradiIstvan Toth

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Citations

Jan 21, 2016·Expert Opinion on Drug Delivery·Pegah Varamini, Istvan Toth
Mar 9, 2021·Drug Discovery Today·Anjali K Pandya, Vandana B Patravale
Jul 17, 2019·Current Medicinal Chemistry·Haralambos TzoupisTheodore Tselios

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