Renal disease
Recurrent stroke prevention
New studies
Mechanism Of Action
Angiotensinogen
Renin
Kidney
Angiotensin I
Alternative pathway (Chymase)
Inactive Prorenin
Bradykinin
ACE
Angiotensin II
Inactive fragments
Active Prorenin
ARB
AT1R
CNS Vascular Edothelium Cardiac Smooth (myocrdial) cells muscle
AT2R
Adrenal cortex
Prorenin receptor
Sympathetic activation
Sodium retention
Kaplans Clinical Hypertension, 2010
Pharmacokinetic
4 sites - candesartan
Hydrogen bonds between ligand and receptor are shown as red dotted lines with hydrogen bond lengths. Carbon atoms of the ligands are coloured light blue and those of the receptors are green
Bhuiyan et al 2009
olmesartan
candesartan
60
40
irbesartan
EXP 3174
valsartan
20
losartan
0 0 20 40
Dissociation t1/2
60
80
100
120
Van Liefde et al 2009
EFIKASI
PENURUNAN TEKANAN DARAH
Candesartan Losartan
8-16 mg 50-100 mg
Irbesartan
150-300 mg
Valsartan
80 mg
Range of trough-to-peak ratio at once daily dosinhg (pacebo adjusted) as measured in various studies (DBP)1 Gordon McInnes. Pocket Reference to Angiotensin II Antagonists. Science Press
Candesartan Cilexetil vs Losartan : Mean Change From Baseline to Week 8 in Systolic ABP
Hours after dose 12 14 16 18 20 22 24 26 28 30 32 34 36
-2
-4 -6 -8 -10 -12 -14
Losartan 100mg
p=0.004
Candesartan cilexetil 16mg -16 Maintenance of control of blood pressure fully and consistently throughout 24 h -18 Maintenance of control of blood pressure beyond 24 h despite poor compliance with Change in SBP (mm Hg) treatment
Lacourcire & Asmar 1999
-2
Losartan Valsartan Irbesartan
-4
-6
Candesartan
0 0 0 0 25 80 75 4 50 160 150 8 100 mg 320 mg 300 mg 16 mg Losartan Valsartan Irbesartan Candesartan
Elmfeldt et al 2002
Effect of Switching from Telmisartan, Valsartan, Olmesartan, or Losartan to Candesartan on Morning Hypertension
Hiroshi Hasegawa,1 Hiroyuki Takano,1 Yoshihito Kameda,1 Akihiko Kubota,1 Yoshio Kobayashi,1 Issei Komuro2 1Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan, 2Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Method:
Seventy-eight mild to moderate hypertensive patients, who were treated with the standard doses of ARBs except candesartan (losartan, 50 mg; valsartan, 80 mg;
To control morning BPs, well-tolerated antihypertensive agents with long durations of action are required.
Candesartan treatment significantly reduced the morning and office BPs compared with other ARBs in Japanese patients with morning hypertension.
TROPHY
TRial Of Preventing HYpertension
TROPHY : Study objectives
TROPHY evaluated 2 years of treatment with candesartan in individuals with prehypertension* Primary objective: Determine if the incidence of HTN can be reduced for up to 2 years after discontinuation of active treatment Secondary objective:
Non-pharmacological treatment
Qualifying period*
Non-pharmacological treatment
Candesartan cilexetil 16 mg daily Placebo
n 400
Two Years
Two Years
OBJECTIVE: The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker (ARB) candesartan (8 mg OD in the morning) can reduce the risk of stroke in elderly patients with isolated systolic
hypertension (ISH).
SCOPE
Candesartan mampu menurunkan risiko stroke (fatal dan non fatal) sebesar 42%
Metode: 269 patients who had persistent proteinuria (1 g/d) despite 7 wk of treatment with the highest approved dosage of candesartan (16 mg/d) to 16, 64, or 128 mg/d candesartan for 30 wk
Objective:
To evaluated whether supramaximal dosages of candesartan would
Relative Effects of Telmisartan, Candesartan and Losartan on Alleviating Arterial Stiffness in Patients with Hypertension Complicated by Diabetes Mellitus: An Evaluation Using the Cardio Ankle Vascular Index
Method
95 pasien hipertensi-DM tipe II ditreatment selama 12 bulan dengan telmisartan 40mg/hari (n=31), candesartan 8mg/hari (n=40) atau losartan 50mg/hari (n=24) Evaluation
Candesartan is a potentially useful therapy against arterial stifness in hypertensive patients with type 2 diabetes mellitus
Comparison of Anti-arteriosclerotic Effects of Candesartan and Valsartan in Type 2 Diabetic Patients with Hypertension Evaluation by Flow-mediated Dilatation (FMD)
Auteur(s) / Author(s) UEHARA Goro ; MORI Kanako ; SAKAI Takako ; MORITA Yasuko ; TAKEDA Hiroshi ;
Rsum / Abstract Objective To compare the effects of candesartan and valsartan on endothelial function assessed by measurement of flow-mediated vasodilation (FMD) in type 2 diabetes patients with hypertension. Methods Subjects who were receiving treatment with valsartan prior to registration were switched to candesartan 8 mg/day (VC group, n=21) whereas those who were receiving candesartan were switched to valsartan 80 mg/day (CV group, n=19) for an observation period lasting 3 months. Percent FMD, blood pressure, and HbA1c were examined at baseline and 3 months after starting treatment. Results The two groups did not differ in terms of patients' baseline clinical characteristics and laboratory data. At 3 months, there were no significant changes in blood pressure and HbA1c in both groups. In the VC group percent FMD significantly increased at 3 months (from 4.7% to 5.8% ; p<0.001), while in the CV group it significantly decreased (from 4.7% to 4.3% ; p<0.001). Moreover, percent FMD at 3 months in the VC group was significantly higher than that in the CV group (p< 0.05). Conclusions This study indicates that suppression of progression of endothelial dysfunction by
Profil Lipid
Pemakaian Candesartan
Hellenic J Cardiol, 2006, Effects of Antihypertensive Treatment with Angiotensin II Receptor Blockers on Lipid Profile
CHARM is the only study to provide clear evidence of the effects of an ARB in preventing DM in heart failure patients, most of whom were receiving a diuretic
Treatment with candesartan reduced the incidence of new- onset diabetes in patients with heart failure by 22%
Mean plasma concentration-time profiles of candesartan in human subjects (n=24) after oral administration of 16 mg candesartan cilexetil tablet produced by PT Dexa Medica (Test Drug = Candesartan Cilexetil 16 mg) and the Reference (Reference Drug = Blopress 16 mg)
16 mg Candesartan cilexetil tablets produced by PT Dexa Medica and the Reference (BLOPRESS 16mg, PT Takeda Indonesia - Indonesia) are BIOEQUIVALENT
PROFILE PRODUCT
INDIKASI
HIPERTENSI Pengobatan pada pasien dengan gagal jantung dan gangguan fungsi sistolik ventrikel kiri (LVEF < 40%) ketika obat penghambat ACE tidak ditolelir
KONTRAINDIKASI
Penderita yang sensitif terhadap komponen CANDERIN. Wanita hamil dan menyusui Kerusakan hati yang berat dan/atau kolestasis
Kesimpulan
Pharmacokinetics
Afinitas lebih tinggi, durasi ikatan lebih panjang Efikasi: Penurunan tekanan darah lebih baik Efek proteksi terhadap ginjal, otak, jantung Pleiotropic effect: menurunkan kekakuan arteri, memperbaiki profil lipid Aman untuk pasien asma Bioekivalen dengan originator Lebih cost effective
Pharmacodinamics
Tolerability
PRODUK
2013
Terima kasih atas dukungan dan kepercayaan dokter terhadap produk-produk PT Dexa Medica
http://cme.medicinus.co/
Untuk berlangganan hubungi: Email: manenda.rossi@dexa-medica.com (u.p. Ninda)/ medical@dexa-medica.com