A prodrug form of olmesartan
Olmesartan medoxomil, the medoxomil ester of olmesartan, is novel and oral antagonist of angiotensin II TYPE-1 receptor (AT1 receptor) with an inhibition constant IC50 of 33 nmol/L. Through oral administration, olmesartan medoxomil is rapidly absorbed by the gastrointestinal tract converting to its active metabolite olmesartan, whose inhibition constant IC50 towards AT1 receptor is 8 nmol/L. The esterification of olmesartan with medoxomil moiety is just to improve its water solubility (from 4.5% to 28.6%). Olmesartan medoxomil is used for the treatment of hypertension, in which olmesartan dose-dependently reduces the blood pressure through arterial vasodilation and reducing sodium retention.
Reference
[1].HR Brunner. The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview. Journal of Human Hypertension (2002) 16 (Suppl 2), S13-S16
[2].Shailesh T. Prajapati, Hitesh H. Bulchandani, Dashrath M. Patel, Suresh K. Dumaniya and Chhaganbhai N. Patel. Formulation and evaluation of liquisolid compacts for olmesartan medoxomil. Journal of Drug Delivery 2013.
Animal experiment: | Mice[3]10 to 12-week old male db/db diabetic mice with background strain C57BL/KsJ and their age-matched non-diabetic lean control mice (C57BL) are used.10 non-diabetic control mice and 10 diabetic mice are fed with placebo (0.5% sodium CMC/saline solution), and 10 diabetic mice are fed with 20 mg/kg Olmesartan (MB5704) by daily gavage for 12 weeks. Mice are monitored for blood glucose, body weight and urine output every two weeks. After treatment, mice are euthanized and trunk blood is collected and is centrifuged to obtain plasma which is aliquoted and stored at -80°C. Kidney tissues are removed from mice. For protein extraction slices of the kidney tissue are frozen in liquid nitrogen, and stored at -80°C. Other parts of the kidney tissue are fixed with 4% paraformaldehyde and embedded in paraffin for immunostaining. |
参考文献: [1]. Senda A, et al. Effects of Angiotensin II Receptor Blockers on Metabolism of Arachidonic Acid via CYP2C8. Biol Pharm Bull. 2015;38(12):1975-9. | |
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