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Candesartan

Antihypertensive Agents
CATEGORIES

Antihypertensive Agents, Angiotensin II Type 1 Receptor Blockers, Angiotensin Receptor Antagonists


ALIASES

Amias, Atacand, Atacand Plus, Atacand®, Atacand® Plus, Blopresid Comp, Blopress Comp, Candemox Comp, Candesarstad, Candesarstad Comp, Candesartan Actavis, Candesartan Krka, Candesartan Navamedic, Candesartan Orion, Candesartan Ranbaxy, Candesartan Sandoz, Candesartan/Hydrochlorothiazide 2care4, Candesartan/Hydrochlorothiazide Actavis, Candesartan/Hydrochlorothiazide Krka, Candesartan/Hydrochlorothiazide Navamedic, Candesartan/Hydrochlorothiazide Orion, Candesartan/Hydrochlorothiazide STADA, Candesartan/Hydrochlorothiazide Teva, Candexetil, Candexetil comp, Kairasec, Kandrozid, Racanda, Ratacand, Ratacand Plus


SUBSTANCES

candesartan, candesartan cilexetil


ENVIRONMENTAL CONCERN: MODERATE
Candesartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. It is administered orally as the prodrug, candesartan cilexetil, which is rapidly converted to its active metabolite, candesartan, during absorption in the gastrointestinal tract. Candesartan lowers blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); it competes with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Candesartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.

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MODERATE
Data on environmental measurements are missing. Candesartan is potentially persistent. Effectstudies of candesartan indicate low toxicity (> 1mg/L) in aquatic organisms. However, studies in aquatic organisms on the expected effects according to mechanisms of the substance are lacking.

In the literature there are contradictory fat solubility data reported for candesartan. However, several independent sources report an estimated fat solubility (logPow) above 4, indicating that the substance has a high potential for bioaccumulation.

Comparison with irbesartan:
Irbesartan is included in the Stockholm County Council's table of pharmaceuticals with risk for negative environmental impact according to the environmental program 2017-2021, inter alia based on irbesartan being found in surface water at levels that are expected to bioconcentrate in fish to therapeutic concentrations. Irbesartan has also been analyzed in single studied fishes, but at levels lower than therapeutic. Measurements of irbesartan in in- and outgoing wastewater in three wastewater treatment plants in Stockholm indicate that irbesartan is not purified from the wastewater but passes straight into the waterways. In Swedish surface water, up to 56 ng/L have been found.

Candesartan has not been studied in the environment, and there is contradictory fat solubility data for both candesartan and irbesartan, and thus it is difficult to assess the risk of bioaccumulation in aquatic species. The fact that irbesartan is found in wild Swedish fish speaks that irbesartan has the potential to bioaccumulate. Therefore, it is difficult at this time to rank these pharmaceuticals in terms of environmental risk.

The risk classification insignificant, according to Fass.se, is based on total sold amount (kg) of the substance in Sweden during the year 2014 and the toxicity of the substance.

REFERENCES

  1. Fass.se för vårdpersonal
  2. UBA, The Umweltbundesamt. Database - Pharmaceuticals in the environment.
  3. Schulz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie. 2003;58:447-74.
  4. Fick J, Lindberg RH, Tysklind M, Larsson DG. Predicted critical environmental concentrations for 500 pharmaceuticals. Regul Toxicol Pharmacol. 2010;58:516-23.
  5. Stockholms läns landsting. Förteckning över miljöbelastande läkemedel inklusive åtgärdsförslag framtagen inom ramen för SLL:s miljöprogram 2017–2021.