Tìm theo
Conivaptan
Các tên gọi khác (2) :
  • 4'-((4,5-dihydro-2-Methylimidazo(4,5-D)(1)benzazepin-6(1H)-yl)carbonyl)-2-biphenylcarboxanilide
  • Conivaptan
Thuốc Gốc
Small Molecule
CAS: 210101-16-9
ATC: C03XA02
ĐG : Astellas Pharma Inc. , http://www.astellas.com
CTHH: C32H26N4O2
PTK: 498.5744
Conivaptan is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C32H26N4O2
Phân tử khối
498.5744
Monoisotopic mass
498.205576096
InChI
InChI=1S/C32H26N4O2/c1-21-33-28-19-20-36(29-14-8-7-13-27(29)30(28)34-21)32(38)23-15-17-24(18-16-23)35-31(37)26-12-6-5-11-25(26)22-9-3-2-4-10-22/h2-18H,19-20H2,1H3,(H,33,34)(H,35,37)
InChI Key
InChIKey=IKENVDNFQMCRTR-UHFFFAOYSA-N
IUPAC Name
N-[4-({4-methyl-3,5,9-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),2(6),3,11,13-pentaen-9-yl}carbonyl)phenyl]-2-phenylbenzamide
Traditional IUPAC Name
N-[4-({4-methyl-3,5,9-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),2(6),3,11,13-pentaen-9-yl}carbonyl)phenyl]-2-phenylbenzamide
SMILES
CC1=NC2=C(CCN(C(=O)C3=CC=C(NC(=O)C4=CC=CC=C4C4=CC=CC=C4)C=C3)C3=CC=CC=C23)N1
Độ hòa tan
Very slightly soluble (0.15 mg/mL at 23 °C)
logP
6.3
logS
-5.5
pKa (strongest acidic)
11.14
pKa (Strongest Basic)
6.23
PSA
78.09 Å2
Refractivity
150.83 m3·mol-1
Polarizability
55.51 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
3
H Bond Donor Count
2
Physiological Charge
0
Number of Rings
6
Bioavailability
1
Dược Lực Học : Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1A and V2 receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular 1A receptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2 antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V1A receptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality.
Cơ Chế Tác Dụng : Conivaptan is a non-peptide inhibitor of antidiuretic hormone (vasopressin). It was approved in 2004 for hyponatremia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH). Conivaptan inhibits both isotypes of the vasopressin receptor (V1a and V2). Conivaptan is a dual AVP antagonist with nanomolar affinity for human arginine vasopressin V1A and V2 receptors in vitro. This antagonism occurs in the renal collecting ducts, resulting in aquaresis, or excretion of free water.
Dược Động Học :

▧ Protein binding :
99%
▧ Metabolism :
CYP3A4 is the sole cytochrome P450 isozyme responsible for the metabolism of conivaptan. Four metabolites have been identified. The pharmacological activity of the metabolites at V1a and V2 receptors ranged from approximately 3-50% and 50-100% that of conivaptan, respectively.
▧ Half Life :
5 hours
Độc Tính : Although no data on overdosage in humans are available, conivaptan has been administered as a 20 mg loading dose on Day 1 followed by continuous infusion of 80 mg/day for 4 days in hyponatremia patients and up to 120 mg/day for 2 days in CHF patients. No new toxicities were identified at these higher doses, but adverse events related to the pharmacologic activity of conivaptan, e.g. hypotension and thirst, occurred more frequently at these higher doses.
Chỉ Định : For the treatment of euvolemic or hypervolemic hyponatremia (e.g. the syndrome of inappropriate secretion of antidiuretic hormone, or in the setting of hypothyroidism, adrenal insufficiency, pulmonary disorders, etc.) in hospitalized patients.
Tương Tác Thuốc :
  • Alfuzosin CYP3A4 Inhibitors (Strong) may increase the serum concentration of Alfuzosin. Concomitant use of alfuzosin with a strong CYP3A4 inhibitor is a listed contraindication according to alfuzosin prescribing information.
  • Almotriptan CYP3A4 Inhibitors (Strong) may increase the serum concentration of Almotriptan. Use an initial almotriptan dose of 6.25mg when using almotriptan with a strong CYP3A4 inhibitor, and do not exceed 12.5mg of almotriptan in any 24-hour period. Avoid concurrent use of almotriptan with a strong CYP3A4 inhibitor in patients with impaired hepatic or renal function.
  • Artemether Conivaptan, a strong CYP3A inhibitor, may increase the toxicity of artemether by inhibiting its metabolism. Consider alternate therapy or allow at least 7 days to elapse between conivaptan and artemether therapy.
  • Bexarotene Conivaptan may increase the serum concentration of CYP3A4 substrates such as bexarotene. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Consider therapy modification.
  • Bezafibrate Conivaptan may increase the serum concentration of CYP3A4 substrates like bezafibrates. Consider therapy modification. Conivaptan may increase the serum concentration of CYP3A4 substrates.
  • Boceprevir Boceprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Bromazepam Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if conivaptan is initiated, discontinued or dose changed. Dosage adjustments may be required.
  • Budesonide CYP3A4 Inhibitors (Strong) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). onsider reducing the oral budesonide dose when used together with a strong CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Any patient receiving both budesonide and a strong CYP3A4 inhibitor should be monitored closely for signs/symptoms of corticosteroid excess.
  • Bupivacaine Conivaptan may increase the serum concentration of CYP3A4 Substrates such as bupivacaine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
  • Buprenorphine Conivaptan may increase the serum concentration of CYP3A4 Substrates like buprenorphine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
  • Caffeine Conivaptan may increase the serum concentration of CYP3A4 substrates such as caffeine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
  • Cevimeline Conivaptan may increase the serum concentration of CYP3A4 substrates such as cevimeline. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
  • Colchicine CYP3A4 Inhibitors (Strong) may increase the serum concentration of Colchicine. In patients with normal renal and hepatic function, reduce colchicine dose (for gout flares: to 0.6 mg x 1 dose, followed by 0.3 mg 1 hour later, with next dose no sooner than 3 days later; for gout flare prophylaxis: if target dose would otherwise be 0.6 mg daily, change to 0.3 mg every other day, and if target dose would otherwise be 0.6 mg twice daily, change to 0.3 mg daily; for Familial Mediterranean Fever: to no more than 0.6 mg/day) when using in combination with a strong CYP3A4 inhibitor such as clarithromycin or ritonavir. Increase monitoring for colchicine-related toxicity when using such combinations. Colchicine use is contraindicated in patients with impaired renal and/or hepatic function who are also receiving a strong CYP3A4 inhibitor.
  • Dantrolene Conivaptan may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if conivaptan is initiated, discontinued or dose changed.
  • Dronedarone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Dronedarone. Concurrent use of strong CYP3A4 inhibitors with dronedarone is contraindicated according to dronedarone prescribing information.
  • Eplerenone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Eplerenone. The combination of eplerenone with any strong CYP3A4 inhibitor is contraindicated.
  • Everolimus CYP3A4 Inhibitors (Strong) may increase the serum concentration of Everolimus. Everolimus prescribing information recommends avoiding concurrent use with strong CYP3A4 inhbitors.
  • Fentanyl CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fentanyl. Concurrent use of fentanyl with any CYP3A4 inhibitor may result in increased fentanyl concentrations and could increase or prolong adverse effects, including potentially fatal respiratory depression. Patients receiving fentanyl and any CYP3A4 inhibitor should be closely monitored for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate.
  • Fesoterodine CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Fesoterodine. Avoid fesoterodine doses greater than 4mg daily in patients who are also receiving strong CYP3A4 inhibitors.
  • Fluconazole Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
  • Fluticasone Propionate CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
  • Halofantrine CYP3A4 Inhibitors (Strong) may increase the serum concentration of Fluticasone (Oral Inhalation). Concurrent use of orally inhaled fluticasone with strong CYP3A4 inhibitors is not recommended.
  • Iloperidone CYP3A4 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Iloperidone. Specifically, concentrations of the metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Iloperidone. Reduce iloperidone dose by half when administered with a strong CYP3A4 inhibitor.
  • Itraconazole Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
  • Ixabepilone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ixabepilone. The dose of ixabepilone must be reduced when used with strong inhibitors of CYP3A.1 In one published abstract, ixabepilone 20mg/m2 was the maximum tolerated dose in patients who were also receiving the CYP3A-inhibitor ketoconazole (400mg).
  • Ketoconazole Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
  • Lurasidone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Lurasidone. Avoid use of lurasidone in patients receiving strong CYP3A4 inhibitors.
  • Maraviroc CYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc. When used with a strong CYP3A4 inhibitor, the adult dose of maraviroc should be decreased to 150 mg twice daily. Maraviroc is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min) receiving a strong CYP3A4 inhibitor. Maraviroc may be administered at a dose of 300 mg twice daily with concomitant tipranavir/ritonavir but not with other ritonavir combinations.
  • Methylprednisolone CYP3A4 Inhibitors (Strong) may increase the serum concentration of Methylprednisolone. Consider methylprednisolone dose titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors) and monitor for increased steroid related adverse effects.
  • Nilotinib CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nilotinib. Nilotinib prescribing information recommends avoiding concurrent use of nilotinib with strong inhibitors of CYP3A4.
  • Nisoldipine CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid concurrent use of nisoldipine with strong inhibitors of CYP3A4, as the combination may lead to substantial increases in nisoldipine concentrations.
  • Paclitaxel Avoid combination because it will likely increase the serum concentration of CYP3A4 substrates.
  • Pazopanib CYP3A4 Inhibitors (Strong) may increase the serum concentration of Pazopanib. Avoid concurrent use of pazopanib with strong inhibitors of CYP3A4 whenever possible. If it is not possible to avoid such a combination, reduce pazopanib dose to 400 mg. Further dose reductions may also be required.
  • Ponatinib Strong CYP3A4 inhibitors may increase levels of ponatinib. Monitor concomitant therapy closely.
  • Posaconazole Antifungal Agents (Azole Derivatives, Systemic) may decrease the metabolism of Conivaptan. Concomitant use of conivaptan with strong CYP3A4 inhibitors (e.g., azole antifungals) is contraindicated.
  • Ranolazine CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ranolazine. The manufacturer contraindicates the use of ranolazine and strong CYP3A4 inhibitors (such as the azole antifungals).1 Monitor for increased effects/toxicity of ranolazine during concomitant use.
  • Rivaroxaban CYP3A4 Inhibitors (Strong) may increase the serum concentration of Rivaroxaban. Consider avoiding use of rivaroxaban with any strong CYP3A4 inhibitors as many such agents are inhibitors of both CYP3A4 and P-glycoprotein. Use of rivaroxaban concomitantly with drugs that are strong inhibitors of both CYP3A4 and P-glycoprotein is specifically contraindicated.
  • Romidepsin CYP3A4 Inhibitors (Strong) may increase the serum concentration of Romidepsin. Avoid concurrent use of strong CYP3A4 inhibitors with romidepsin when possible.
  • Salmeterol CYP3A4 Inhibitors (Strong) may increase the serum concentration of Salmeterol. Concurrent use of salmeterol with strong inhibitors of CYP3A4 is not recommended according to salmeterol prescribing information.
  • Saxagliptin CYP3A4 Inhibitors (Strong) may increase the serum concentration of Saxagliptin. Limit saxagliptin dose to 2.5 mg/day and monitor for increased saxagliptin levels/effects (e.g., hypoglycemia) with concomitant administration of a strong CYP3A4 inhibitor (e.g., ketoconazole). Monitor for decreased saxagliptin levels/effects with discontinuation of concomitant CYP3A4 inhibitor.
  • Sildenafil CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Sildenafil. When sildenanfil is used for treatment of pulmonary arterial hypertension, concurrent use with strong CYP3A4 inhibitors is not recommended. When sildenafil is used for treatment of erectile dysfunction, consider using a lower starting dose of 25 mg in patients who are also taking a strong CYP3A4 inhibitor. Due to the particularly strong effects of ritonavir, sildenafil (for erectile dysfunction) doses greater than 25 mg per 48 hours are not recommended. Of note, the interaction between CYP3A4 inhibitors and sildenafil is predicted to be greater with orally administered than with injected sildenafil.
  • Silodosin CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Silodosin. Use of silodosin concomitantly with a strong CYP3A4 inhibitor is contraindicated.
  • Tacrolimus The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Conivaptan is initiated, discontinued or dose changed.
  • Tadalafil Conivaptan may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
  • Tamoxifen Conivaptan may increase the serum concentration of Tamoxifen by decreasing its metabolism. Monitor for increased adverse/toxic effects of Tamoxifen.
  • Tamsulosin Conivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Conivaptan is initiated, discontinued, or dose changed.
  • Telaprevir Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
  • Telithromycin Co-administration may result in altered plasma concentrations of Conivaptan and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
  • Temsirolimus Conivaptan may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
  • Teniposide The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Conivaptan is initiated, discontinued or dose changed.
  • Tiagabine The strong CYP3A4 inhibitor, Conivaptan, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Conivaptan is initiated, discontinued or dose changed.
  • Ticagrelor CYP3A4 Inhibitors (Strong) such as conivaptan may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Avoid use of ticagrelor in combination with strong CYP3A4 inhibitors.
  • Tolterodine Conivaptan may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
  • Tolvaptan CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Tolvaptan. Coadministration of a strong CYP3A4 inhibitor with tolvaptan is contraindicated.
  • Toremifene CYP3A4 Inhibitors (Strong) such as conivaptan may enhance the adverse/toxic effect of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Toremifene. Concurrent use of toremifene with strong CYP3A4 inhibitors should be avoided.
  • Tramadol Conivaptan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
  • Trazodone The CYP3A4 inhibitor, Conivaptan, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Conivaptan is initiated, discontinued or dose changed.
  • Vardenafil Conivaptan, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
  • Venlafaxine Conivaptan, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Conivaptan is initiated, discontinued, or dose changed.
  • Verapamil Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Conivaptan is initiated, discontinued or dose changed.
  • Vilazodone CYP3A4 Inhibitors (Strong) such as conivaptan may increase the serum concentration of Vilazodone. Limit maximum adult vilazodone dose to 20 mg/day in patients receiving strong CYP3A4 inhibitors.
  • Vinblastine Conivaptan, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Conivaptan is initiated, discontinued or dose changed.
  • Vincristine Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Conivaptan is initiated, discontinued or dose changed.
  • Vinorelbine Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Conivaptan is initiated, discontinued or dose changed.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of conivaptan by inhibiting its metabolism. Concomitant therapy is contraindicated.
  • Zolpidem Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zolpidem by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zolpidem if conivaptan is initiated, discontinued or dose changed.
  • Zonisamide Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if conivaptan is initiated, discontinued or dose changed.
  • Zopiclone Conivaptan, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if conivaptan is initiated, discontinued or dose changed.
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    Sản phẩm biệt dược : Vaprisol
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00872
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=151171
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504533
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01236
ChemSpider
http://www.chemspider.com/Chemical-Structure.133239.html
PharmGKB
http://www.pharmgkb.org/drug/PA164742939
Wikipedia
http://en.wikipedia.org/wiki/Conivaptan
Drugs.com
http://www.drugs.com/cdi/conivaptan.html
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