Delving into the Latest Updates on Hydrochlorothiazide/Valsartan with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Co-Dio, Co-Diovan, Co-Tareg

+ [26]

Target

AT1R x NCC

Action

antagonists, inhibitors

Mechanism

AT1R antagonists(Angiotensin II Receptor Type 1 antagonists), NCC inhibitors(Thiazide-sensitive sodium-chloride cotransporter inhibitors)

Therapeutic Areas

Cardiovascular Diseases

Active Indication

Hypertension

Inactive Indication

Essential Hypertension

Originator Organization

Novartis Pharma AG

Active Organization

Novartis Pharmaceuticals Corp.Novartis Pharma AGNovartis Pharmaceuticals Australia Pty Ltd.

Inactive Organization

Novartis AG

Changzhou Siyao Pharmaceuticals Co. Ltd.

License Organization-

Drug Highest PhaseApproved

First Approval Date

United States (06 Mar 1998),

Hypertension

RegulationPriority Review (China)

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Structure/Sequence

Molecular FormulaC31H37ClN8O7S2

InChIKeyUIYUUEDFAMZISF-FTBISJDPSA-N

CAS Registry186615-83-8

Hypertension is a major global health problem, affecting about 30% of people and up to two-thirds of those over 60 years. Its prevalence has increased significantly, with over one billion adults affected worldwide and expected to reach 1.56 billion by 2025, especially in developing countries where early diagnosis and treatment are limited. Long-term hypertension can lead to hypertensive heart disease (HHD), which includes left ventricular hypertrophy and increases the risk of stroke, heart attack, heart failure, and kidney disease. Diagnosis is based on clinical assessment along with ECG, echocardiography, and cardiac MRI.
Management focuses on controlling blood pressure and preventing heart damage. Valsartan, an angiotensin receptor blocker, and hydrochlorothiazide, a thiazide diuretic, are commonly used treatments. Studies suggest that combining these drugs may be more effective than valsartan alone, with better outcomes and fewer side effects. However, local evidence in Pakistan is limited.
This study aims to compare valsartan plus hydrochlorothiazide versus valsartan alone in patients with HHD. A randomized controlled trial will be conducted at Sheikh Zayed Hospital, Lahore, including 118 patients aged 18-70 years diagnosed with HHD. Participants will be divided into two groups: one receiving combination therapy and the other valsartan alone for eight weeks, with dose adjustments as needed.
Effectiveness will be classified as effective or ineffective. Patient data, including age, gender, BMI, and disease duration, will be analyzed using SPSS version 26. Results will be compared using the chi-square test, with further analysis to control confounding factors.
This study will help determine the better treatment option and support improved management of hypertension in Pakistan.

Start Date01 Nov 2025

Sponsor / Collaborator

Shaikh Zayed Hospital

CTR20241901

/ CompletedNot Applicable

缬沙坦氢氯噻嗪片在中国健康受试者中空腹和餐后单次口服给药、随机、开放、两制剂、三序列、三周期、部分重复交叉生物等效性试验

[Translation] A single oral fasting and postprandial randomized, open-label, two-dose, three-sequence, three-period, partially repeated crossover bioequivalence study of valsartan and hydrochlorothiazide tablets in healthy Chinese volunteers

主要目的：评价在健康受试者中空腹和餐后单次口服受试制剂（缬沙坦氢氯噻嗪片，深圳奥萨制药有限公司，规格：每片含缬沙坦80 mg，氢氯噻嗪12.5 mg）与参比制剂（复代文®，Novartis Pharma Schweiz AG，规格：每片含缬沙坦80 mg，氢氯噻嗪12.5 mg）的生物等效性。次要目的：观察空腹和餐后口服受试制剂和参比制剂的安全性。

[Translation]

Primary objective: To evaluate the bioequivalence of a single oral dose of the test formulation (valsartan hydrochlorothiazide tablets, Shenzhen Osa Pharmaceutical Co., Ltd., specifications: each tablet contains 80 mg valsartan and 12.5 mg hydrochlorothiazide) and a reference formulation (CoDiovan®, Novartis Pharma Schweiz AG, specifications: each tablet contains 80 mg valsartan and 12.5 mg hydrochlorothiazide) in healthy subjects on an empty stomach and after a meal. Secondary objective: To observe the safety of the test formulation and the reference formulation when taken orally on an empty stomach and after a meal.

Start Date29 May 2024

Sponsor / Collaborator

Shenzhen Osa Pharmaceutical Co., Ltd.

CTR20240954

/ CompletedNot Applicable

健康受试者在空腹和餐后状态下单次口服缬沙坦氢氯噻嗪片的随机、开放、两序列、两制剂、四周期、完全重复交叉的生物等效性试验

[Translation] A randomized, open-label, two-sequence, two-formulation, four-period, completely repeated crossover bioequivalence study of a single oral dose of valsartan and hydrochlorothiazide tablets in healthy subjects in the fasting and fed state

主要研究目的：试验空腹和餐后状态下单次口服受试制剂缬沙坦氢氯噻嗪片（规格：80/12.5mg（每片含缬沙坦80mg，氢氯噻嗪12.5mg），浙江金立源药业有限公司）与参比制剂缬沙坦氢氯噻嗪片（Co-Diovan®，规格：80/12.5mg（每片含缬沙坦80mg，氢氯噻嗪12.5mg），Novartis Farma S.p.A.(I)生产）在健康成年受试者体内的药代动力学，评价空腹和餐后状态口服两种制剂的生物等效性。次要研究目的：评价健康受试者在空腹和餐后状态下，单次口服缬沙坦氢氯噻嗪片受试制剂和参比制剂后的安全性。

[Translation]

The main purpose of the study is to test the pharmacokinetics of the test preparation valsartan hydrochlorothiazide tablets (specification: 80/12.5mg (each tablet contains 80mg valsartan and 12.5mg hydrochlorothiazide), Zhejiang Jinliyuan Pharmaceutical Co., Ltd.) and the reference preparation valsartan hydrochlorothiazide tablets (Co-Diovan®, specification: 80/12.5mg (each tablet contains 80mg valsartan and 12.5mg hydrochlorothiazide), produced by Novartis Farma S.p.A. (I)) in healthy adult subjects after a single oral administration in the fasting and fed state, and to evaluate the bioequivalence of the two preparations after oral administration in the fasting and fed state. Secondary purpose of the study: to evaluate the safety of the test preparation and reference preparation of valsartan hydrochlorothiazide tablets in healthy subjects after a single oral administration in the fasting and fed state.

Start Date29 May 2024

Sponsor / Collaborator

Zhejiang Kinglyuan Pharmaceutical Co. Ltd.

100 Clinical Results associated with Hydrochlorothiazide/Valsartan

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100 Translational Medicine associated with Hydrochlorothiazide/Valsartan

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100 Patents (Medical) associated with Hydrochlorothiazide/Valsartan

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21

Literatures (Medical) associated with Hydrochlorothiazide/Valsartan

01 Jan 2026·EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

In vitro two stage one compartment dumping test data and absorption/formulation PBBM modeling to explain a bioequivalence failure of valsartan formulations

Article

Author: Gonzalez-Alvarez, Isabel ; Ruiz-Picazo, Alejandro ; Sánchez-Dengra, Bárbara ; Gonzalez-Alvarez, Marta ; Bermejo, Marival

BACKGROUND:

In recent years, significant efforts have been made to develop new dissolution methods capable of predicting the in vivo behavior of pharmaceutical formulations. This is essential for establishing valid in vitro-in vivo correlations (IVIVCs) and biopredictive models. However, many of these methodologies involve sophisticated, costly, and complex devices designed to replicate human physiology. The objective of this study was to predict in vivo bioequivalence (BE) using a simplified dynamic dissolution methodology and to establish a physiologically based biopharmaceutics model (PBBM).

METHODS:

An oral fixed-dose combination of valsartan (VALS, BCS Class IV) and hydrochlorothiazide (HCTZ, BCS Class III) was used for the study. The reference product (Co-Diovan® Forte) and two generic formulations were evaluated using a dissolution approach. A two stage one compartment dissolution technique, known as the "dumping test," was applied to assess drug release profiles. The in vitro dissolution data obtained were incorporated into the PBBM, with two scaling factors-one for time and another for absorption-to enhance predictive accuracy.

RESULTS:

The "dumping test" successfully simulated the different dissolution behaviors of the formulations and explained the failure of bioequivalence in certain cases. The established IVIVC demonstrated both validity and biopredictive capability. The percentage prediction errors (% PEs) for the PBBM, after incorporating in vitro data and the scaling factors, remained within acceptable regulatory limits.

CONCLUSIONS:

The study demonstrated that a simple dynamic dissolution methodology can effectively predict in vivo bioequivalence and formulation performance. The application of the "dumping test" provided valuable insights into the dissolution characteristics of different formulations, highlighting its potential as a cost-effective and practical tool for biopredictive studies.

01 Feb 2024·PHARMACEUTICAL CHEMISTRY JOURNAL

A Supercritical Fluid Chromatography and Tandem Mass Spectrometry Method for the Simultaneous Quantification of Valsartan and Hydrochlorothiazide in Human Plasma

Author: Prajapati, Prajesh ; Gogoi, Parthajyoti ; Agrawal, Y. K.

A simultaneous rapid, sensitive supercritical fluid chromatog. and tandem mass spectrometry method for the separation and quantification of valsartan (VAL) and hydrochlorothiazide (HCT) is developed and validated.Separation was done in a Nucleosil (250 mm x 4.6 mm) 10 mm, Nucleosil-C₁₈ column with acetonitrile modified supercritical fluid carbon dioxide (15 mL min^-1) as mobile phase.The column temperature was 45°C and the outlet pressure was set at 17 MPa.The analytes were quantitated in neg. ionization by multiple reaction monitoring (MRM) with a mass spectrometer, the mass ionizations m/z 434.2 - 350.2 and m/z 295.9 - 204.9 used to measure VAL and HCT resp.The assay exhibited a linear dynamic range of 3.2 - 3200 ng/mL for VAL and 0.8 - 800 ng/mL for HCT.The method was validated and successfully used for simultaneous determination of drugs in tablets.

01 Mar 2015·Journal of AOAC InternationalQ4 · AGRICULTURAL & FORESTRY SCIENCE

HPTLC with Fluorescence Densitometry for Simultaneous Determination of Some Angiotensin II Receptor Blockers in Tablets and Plasma

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: El-Wadood, Hanaa Mohamed Abd ; Abdallah, Mohamed Abou-El Wafa ; Hussein, Samiha Abd El-Rahman ; Khorshed, A Abd El-Hamid

Abstract:

A selective, accurate, precise, and highly sensitive HPTLC assay with reflectance/fluorescence densitometry was developed to separate and quantify some angiotensin II receptor blockers (ARBs), namely, losartan potassium, irbesartan, valsartan, and olmesartan medoxomil, in tablets and plasma. Separation of the target ARBs was performed on precoated silica gel HPTLC plates developed using chloroform–glacial acetic acid (7.5 + 2.5, v/v) mobile phase. The drugs were adequately resolved. After the exposure of the chromatograms to concentrated hydrochloric acid vapor for 10 min, the scanner was set in the reflectance/fluorescence mode with 255 nm excitation wavelength and >400 nm emission filter. The linear regression analysis data for the calibration curves of all studied drugs produced a good linear relationshipwith correlation coefficients ranging from 0.9991 to0.9999 over the concentration range of 2–20 ng/band. LOD and LOQ values of all studied drugs ranged from 0.6 to 0.8 and from 1.7 to 2.4 ng/band, respectively. The developed method was successfully applied for analysis of the target ARBs in tablets and spiked human plasma samples with good precision and accuracy.

100 Deals associated with Hydrochlorothiazide/Valsartan

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hypertension	United States	Novartis Pharmaceuticals Corp.	06 Mar 1998

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Essential Hypertension	Phase 3	Germany	Novartis AG	01 Dec 2004
Essential Hypertension	Phase 3	Switzerland	Novartis AG	01 Dec 2004

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00171561 (EASD2013)	Phase 4	Diabetes Mellitus, Type 2 \| Albuminuria soluble Klotho \| serum phosphate	-	Valsartan/hydrochlorothiazide	otaedlalks(yusbnxwtax) = hgegxrzluy ewcbkslxkt (ljwlegxtbc, 0.31) View more	Positive	26 Sep 2013
				Amlodipine	otaedlalks(yusbnxwtax) = mvlmdcvkmj ewcbkslxkt (ljwlegxtbc, 0.49) View more
NCT00425997 (Pubmed \| J Clin Hypertens (Greenwich))	Phase 4	Obesity \| Hypertension	401	Combination valsartan/hydrochlorothiazide	pekgnxlnlc(ksnqwrrjsg) = vtvnjarkeg cpusqjelqu (nvurjveroq ) View more	-	01 Oct 2011
				Amlodipine/HCTZ	pekgnxlnlc(ksnqwrrjsg) = smaaimyajw cpusqjelqu (nvurjveroq ) View more
NCT00698646 (Pubmed \| J Clin Hypertens (Greenwich))	Phase 4	Hypertension	384	valsartan/hydrochlorothiazide 160/12.5 mg	aijzrlfgen(nsmbwxdgwh) = djriiqdfeo cumepwjztk (ttsjrelsra ) View more	-	01 Oct 2011
				hydrochlorothiazide 12.5 mg	aijzrlfgen(nsmbwxdgwh) = znjbdqlrqz cumepwjztk (ttsjrelsra ) View more
NCT00698646 (ValVET, CTgov)	Phase 4	Essential Hypertension	384	Valsartan (Valsartan)	ysvbiqmons(ddnadrqeix) = hqrnaagnkd cbxljjznrt (tcejkpzodu, 11.07) View more	-	15 Dec 2010
				HCTZ (HCTZ)	ysvbiqmons(ddnadrqeix) = wwtihdxrud cbxljjznrt (tcejkpzodu, 11.84) View more
NCT00280540 (Pubmed \| J Hum Hypertens)	Phase 4	Hypertension	648	Valsartan 80 mg	kkkugylkqp(iofcxoduub) = Overall and drug-related AEs were mild to moderate and were similar between V/HCTZ (53.1 and 14.1%, respectively) and the two monotherapy groups, V-low (50.5 and 13.8%) and V-high (50.7 and 11.8%) rwejbvtijc (mhdpsjhpui )	Positive	01 Jul 2010
				Valsartan 160 mg
NCT00439738 (CTgov)	Phase 4	Obesity, Abdominal \| Obesity \| Hypertension	412	HCTZ+Amlodipine	lnsozxddej(hwbeuevsxk) = fhxykqtywq rtwdtfluhn (pcmdgqhfsb, 7.62) View more	-	10 Feb 2009
NCT00273299 (Pubmed \| Curr Med Res Opin)	Phase 3	Hypertension	608	Valsartan/HCTZ combination therapy	mzyqqtwror(tddxkzkqhq) = yoiwtaqqgl jasuljyodi (qsazgkiujs ) View more	-	01 Aug 2008
				Valsartan monotherapy	mzyqqtwror(tddxkzkqhq) = tgontilxqj jasuljyodi (qsazgkiujs ) View more
Pubmed \| Curr Med Res Opin	Phase 3	Hypertension	198	Valsartan 160 mg/hydrochlorothiazide 25 mg	ttmpwlatss(riojnznbwc) = mavmndbgxc dxucokuetp (dppkspwniv )	-	01 Nov 2007
				Candesartan 32 mg plus HCTZ 25 mg	ttmpwlatss(riojnznbwc) = otxuodcrgb dxucokuetp (dppkspwniv )