Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C20H26N2O5S2 |
| Molecular Weight | 438.561 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 3 / 3 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N2CC3(C[C@H]2C(O)=O)SCCS3
InChI
InChIKey=FMMDBLMCSDRUPA-BPUTZDHNSA-N
InChI=1S/C20H26N2O5S2/c1-13(21-15(18(24)25)8-7-14-5-3-2-4-6-14)17(23)22-12-20(28-9-10-29-20)11-16(22)19(26)27/h2-6,13,15-16,21H,7-12H2,1H3,(H,24,25)(H,26,27)/t13-,15-,16-/m0/s1
DescriptionCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01348 | https://www.ncbi.nlm.nih.gov/pubmed/18154140 | https://www.ncbi.nlm.nih.gov/pubmed/15490771 | https://www.ncbi.nlm.nih.gov/pubmed/15752941
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01348 | https://www.ncbi.nlm.nih.gov/pubmed/18154140 | https://www.ncbi.nlm.nih.gov/pubmed/15490771 | https://www.ncbi.nlm.nih.gov/pubmed/15752941
Spirapril (Renormax) is an ACE inhibitor antihypertensive drug used to treat hypertension. Spiraprilat, the active metabolite of spirapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Spiraprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
CNS Activity
Originator
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
81.6 μg/L |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SPIRAPRILAT plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
37.85 μg/L |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SPIRAPRILAT plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
846.75 μg × h/L |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SPIRAPRILAT plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
|
152.5 μg × h/L |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SPIRAPRILAT plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.85 h |
6 mg 1 times / day multiple, oral dose: 6 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
SPIRAPRILAT plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
Other AEs: Cough, Dizziness... Other AEs: Cough (3.8%) Sources: Dizziness (5.3%) Fatigue (6%) Headache (9%) Oedema (3%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Oedema | 3% | 24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
| Cough | 3.8% | 24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
| Dizziness | 5.3% | 24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
| Fatigue | 6% | 24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
| Headache | 9% | 24 mg 1 times / day steady, oral (max) Recommended Dose: 24 mg, 1 times / day Route: oral Route: steady Dose: 24 mg, 1 times / day Sources: |
unhealthy, adult n = 133 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: M+F Population Size: 133 Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effect of long-term treatment with an angiotensin-converting enzyme inhibitor on the renin-angiotensin system in spontaneously hypertensive rats. | 1991 Oct |
|
| Renal effects of angiotensin II in normotensive subjects on short-term cilazapril treatment. | 1992 |
|
| Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients. | 1996 |
|
| ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients. | 2001 Dec |
|
| A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension. | 2001 May |
|
| [ACE inhibitor. Effective blood pressure control around the clock]. | 2001 Sep 6 |
|
| [Effect of angiotensin converting enzyme inhibitor spirapril on dimensions of experimental myocardial infarction, development of ischemic tachyarrhythmias, and ischemic adaptation of the heart]. | 2002 |
|
| Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity. | 2002 |
|
| Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. | 2002 |
|
| [Influence of ACE inhibitor spirapril on left ventricular hypertrophy]. | 2002 Dec 5 |
|
| [Blood pressure control must be effective until the next tablet. Infarct is most frequent in the morning]. | 2002 Jan 24 |
|
| [Hypertensive patient with diabetes. "Blood pressure cosmetics" are not enough here]. | 2002 Jun 13 |
|
| [Open trial using ACE inhibitor. Left ventricular hypertrophy diminishes]. | 2002 Nov 28 |
|
| Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy. | 2002 Sep |
|
| Drug interaction of spirapril hydrochloride monohydrate and hydrochlorothiazide. A clinical study to compare the pharmacokinetics after administration of spirapril hydrochloride monohydrate tablets, hydrochlorothiazide tablets and fixed combination bi-layer tablets. | 2003 |
|
| Simultaneous determination of spirapril and spiraprilat in plasma by capillary gas chromatography-mass spectrometry. | 2003 |
|
| [Blood pressure lowering by the ACE-inhibitor spirapril. "24-hour efficacy of real once daily application of spirapril (HERAS Study)"]. | 2003 Oct 2 |
|
| Thermodynamics of non-stoichiometric pharmaceutical hydrates. | 2005 Oct 13 |
|
| Central angiotensin II controls alcohol consumption via its AT1 receptor. | 2005 Sep |
|
| [Rational approach to selection of antihypertensive therapy in persons with metabolic syndrome: efficacy of monotherapy with spirapril and its combination with retard form of nifedipine]. | 2006 |
|
| [Clinical application of spirapril in patients with arterial hypertension combined with chronic obstructive pulmonary disease]. | 2006 |
|
| [Advantages of long-term controlled stepwise therapy of arterial hypertension with the use of angiotensin converting enzyme inhibitor spirapril]. | 2006 |
|
| [Effect of spirapril on remodeling of the heart in patients with mild and moderate arterial hypertension]. | 2007 |
|
| The Lipid lowering and Onset of Renal Disease (LORD) Trial: a randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease. | 2008 Mar 18 |
|
| Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. | 2008 Nov |
|
| Administration-time-dependent effects of spirapril on ambulatory blood pressure in uncomplicated essential hypertension. | 2010 May |
Sample Use Guides
The daily dose is 6 mg, the frequency of application is 1 time / day. After 4-6 weeks, in the absence of a satisfactory therapeutic effect, the dose can be increased.
Route of Administration:
Oral
Pooled human liver microsomes were obtained from Pfizer Global Supply and the tested compounds were acquired from Pfizer Global Material Management. Each incubation contained tested compounds (Spirapril) (1 mkM), microsomes (0.25 lM protein), NADPH regenerating system (1 mM NADP+, 5 mM isocitric acid and 1 unit/ mL isocitric dehydrogenase), MgCl2 (1 mM) and potassium phosphate buffer (100 mM at pH 7.4). This mixture was incubated at 37 _C for 0, 5, 10, 20, 30 and 60 min before quenching with acetonitrile. Control incubations were prepared using the same procedure without adding the catalytic cofactor NADPH. Individual samples were then analyzed in a ‘trap-and-elute’ mode using LC/MS
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NCI_THESAURUS |
C247
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100000083804
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6576
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C076884
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AA-32
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C152419
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Spiraprilat
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3033702
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m10150
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QS56V5Y7EC
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SUB10621MIG
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141522
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ACTIVE MOIETY
