A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of a new potent antihypertensive agent, TCV-116, and its two metabolites (M-I and M-II) in human serum or urine. After pre-treatment of the specimens, the analytes were determined using a column switching technique, except for the metabolites in urine which were determined by gradient elution mode HPLC. The quantitation limits for TCV-116, M-I and M-II were all 0.5 ng/ml in serum, and 0.5, 10 and 110 ng/ml in urine, respectively. The methods were applied to clinical trials of TCV-116.
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Ther Adv Drug Saf
December 2023
Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang 310009, China.
Background: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments.
View Article and Find Full Text PDFJ Pharm Sci
June 2023
Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
Development of prodrugs is a useful strategy to overcome some disadvantages of candidate drugs. Recently, we established a systematic approach to selecting appropriate prodrugs, and validated the utility of this approach using oseltamivir analogues. In this study, the utility of the approach was further examined using candesartan cilexetil and 20 kinds of its analogues having various types of side chain as model compounds.
View Article and Find Full Text PDFMol Pharm
March 2019
Department of Chemistry, Laboratory of Organic Chemistry , National and Kapodistrian University of Athens, Panepistimioupolis, Zografou 15771 , Greece.
Renin-angiotensin aldosterone system inhibitors are for a long time extensively used for the treatment of cardiovascular and renal diseases. AT1 receptor blockers (ARBs or sartans) act as antihypertensive drugs by blocking the octapeptide hormone Angiotensin II to stimulate AT1 receptors. The antihypertensive drug candesartan (CAN) is the active metabolite of candesartan cilexetil (Atacand, CC).
View Article and Find Full Text PDFAAPS PharmSciTech
February 2018
Department of Pharmaceutics, Faculty of Pharmacy, University of Alexandria, El-Khartoum Square, El-Azarita, Alexandria, 21521, Egypt.
The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochemical evaluation was conducted through solubility, dissolution, and stability studies; additionally, ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alkaline pH.
View Article and Find Full Text PDFJ Pharm Biomed Anal
November 2009
Kimika Analitikoa Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea/UPV, P.K. 644, 48080 Bilbo, Basque Country, Spain.
This paper reports the chemometrical optimization and the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-Fluo) method for the simultaneous analysis, in human plasma, of drugs usually combined in cardiovascular therapy. Separation of chlorthalidone (CLTD), valsartan (VAL), valsartan-M1 (VAL-M1), fluvastatin (FLUV) and the internal standard (IS) candesartan cilexetil was performed on a dC18 Atlantis column (100 mm x 3.9 mm, 3 microm) using a gradient with a run time of 15 min.
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