Ramipril excretion

Lactation Several AC Els have been detected in breast milk. Do not administer trandolapril or ramipril to nursing mothers. It is not known whether lisinopril, moexipril, or ramipril is excreted in breast milk. Discontinue nursing or the drug. Chiidren Safety and efficacy have not been established. Use captopril in children only when other measures for controlling BP have not been effective. 

Keilani T, Danesh FR, Schlueter WA, Molteni A, Batile D. A sub-depressor low dose of ramipril lowers urinary protein excretion without increasing plasma potassium. Am J Kidney Dis 1999 33 450-7. 

In rats, ramipril reduced renal lithium clearance and increased fractional lithium reabsorption in association with decreased systolic blood pressure and decreased sodium excretion. These effects were attenuated by icati-bant, a specific bradykinin B2 receptor antagonist (577). 

The extent of oral absorption varies from 25% (li-sinopril) to 75% (captopril). The rate of absorption also varies from 0.5 h (captopril and enalopril) to 7h (lisinopril). Reported volumes of distribution range from 0.7lkg (captopril) to 1.8lkg (lisinopril). All of the ACE inhibitors, except for captopril and lisinopril, are metabolized in the liver to active metabolites. Excretion is via both the urine and the feces. The half-life ranges from 1.3 h (enalapril) to 17h (ramipril). 

Ramipril (altace) Cleavage of the ester moiety by hepatic esterases transforms ramipiil into ramiprilat, an ACE inhibitor that is about as potent as benazeprilat and quinaprilat. Ramipril is absorbed rapidly (peak concentrations of ramipril achieved in 1 hour), and the rate but not extent of its oral absorption (50-60%) is reduced by food. Ramipril is metabolized to ramiprilat and to inactive metabolites (glucuronides of ramipril and ramiprilat and the diketopiperazine ester and acid) that predominantly are excreted by the kidneys. Peak concentrations of ramiprilat in plasma are achieved in about 3 hours. Ramiprilat displays triphasic ehmination kinetics with tj of 2-4 hours,... 

A comparative study of the metabolism and biliary excretion of lisinopril, enalapril, perindopril, and ramipril revealed that whereas neither lisinopril nor enalapril underwent any appreciable metabolism beyond bioactivation of enalapril to enalaprilat, both perindopril and ramipril were extensively metabolized beyond the initial bioactivation. It was proposed that these differences in hepatic metabolism could be explained, in part, by the larger, more hydrophobic rings present on perindopril and ramipril (35). 

Ramipril has been shown to decrease renal lithium excretion in rats. ... 

Barthelmebs M, Grima M, Imbs J-L Ramipril-induced decrease in renal lithium excretion in the rat. BrJPharmacol( 995) 116, 2161-5. 

Not fully understood. It eould be that, as with the ACE inhibitors, angiotensin n reeeptor antagonists inhibit aldosterone secretion, resulting in increased sodium loss by the kidney tubules. This causes lithium retention and thus an increase in lithium levels. However, angiotensin II receptor antagonists have less effect on aldosterone than the ACE inhibitors, making a clinically significant interaction less likely. Animal studies show that ramipril, but not losartan, decreases the excretion of lithium by the kidney, which would support this idea. 

A 40-year-old man with liver cirrhosis and nephrotic syndrome who had been taking losartan for 6 weeks developed severe acute encephalopathy with unconsciousness after the addition of ramipril [31 ]. The authors surmised that dual blockade had suppressed angiotensin II at the level of the proximal tubule leading to inadequate renal excretion of ammonia, precipitating decompensation. 

---