Species Difference in Hydrolysis of an Ester-Type Prodrug of Levodopa in Human and Animal Plasma: Different Contributions of Alpha-1 Acid Glycoprotein
| Autor: | Yoshiyuki Yamaura, Maeda Hitoshi, Jing Bi, Toru Takeo, Haruo Imawaka, Yuka Nakamura, Toru Maruyama, Hiroshi Watanabe, Ayumi Mukunoki, Ken-ichi Nunoya, Naomi Nakagata, Kenta Kono |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Levodopa Serum albumin Pharmaceutical Science Orosomucoid 02 engineering and technology 030226 pharmacology & pharmacy Mice 03 medical and health sciences Hydrolysis Dogs 0302 clinical medicine Species Specificity Drug Discovery medicine Animals Humans Prodrugs Mice Knockout chemistry.chemical_classification biology Chemistry Albumin Esters Prodrug 021001 nanoscience & nanotechnology Blood proteins Healthy Volunteers Rats Biochemistry biology.protein Molecular Medicine Rabbits 0210 nano-technology Glycoprotein medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 19:3450-3450 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.2c00598 |
| Popis: | Previously, we found that ONO-2160, an ester-type prodrug of levodopa (3-hydroxy-l-tyrosine), was mainly hydrolyzed in human plasma by α1-acid glycoprotein (AGP) with a partial contribution of albumin. In this study, we investigated whether ONO-2160 was hydrolyzed in the plasma of preclinical species (dog, rabbit, rat, and mouse) and humans and whether AGP and albumin are involved in its hydrolysis. ONO-2160 was hydrolyzed to some extent in the plasma of all tested species with the order of magnitude mouse > human > rabbit > rat > dog. Except for dogs, ONO-2160 was partially hydrolyzed by animal AGP and albumin. This indicated that, similar to albumin, AGP possesses esterase-like activity in mice, rats, and rabbits, as well as humans. A comparison of the values of intrinsic clearance per milliliter of plasma demonstrated that AGP was the major contributor to the hydrolysis of ONO-2160 in rabbit plasma, whereas albumin was primarily responsible for the hydrolysis of ONO-2160 in mouse plasma. This was confirmed by experiments using AGP-knockout mouse plasma. This study reports the first evidence for the existence of species differences in the hydrolysis of ONO-2160 in plasma related to the different contributions of AGP and albumin. |
| Databáze: | OpenAIRE |
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