ACE inhibition in chronic renal failure and in the treatment of diabetic nephropathy: focus on spirapril.
The management of hypertension and nephropathy, in both diabetes and other forms of renal disease, is usually based on blood pressure reduction through an angiotensin-converting enzyme (ACE) inhibitor-based treatment regimen. With particular respect to the choice of ACE inhibitor drug, there are no definitive direct comparisons in the treatment of renal disease. In terms of blood pressure reduction, however, there is evidence that spirapril is at least as effective as the reference ACE inhibitor, enalapril. However, patients with diabetic nephropathy and/or chronic renal failure are at potential risk from drug accumulation if the preferred agent relies predominantly on glomerular filtration for its elimination. In this respect spirapril may have an advantage because it has been shown that there are no clinically relevant increases in the spirapril(at) concentrations (24 h post-dose) even in the setting of advanced renal failure (creatinine clearance <20 ml/min). Thus, there is no requirement to modify the dose and no concerns about drug accumulation or the potential for exaggerated therapeutic or adverse effects. In summary, an ACE inhibitor drug is seen as an integral component of the drug treatment regimen for patients with nephropathy. Where there is renal failure it may be prudent to administer a drug, such as spirapril, which also has alternative elimination mechanisms.
Jardine
A G
AG
Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Elliott
H L
HL
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002986:Clinical Trials as Topic; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004656:Enalapril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril