General Toxicity Notes
Blood pressure is the best guide to dose and interval. Hypotensive effects magnified by natriuretic agents or sodium depletion. May cause hyperkalemia, metabolic acidosis. Acute renal dysfunction with bilateral or transplant renal artery stenosis, low renal perfusion pressure. Dry cough in 5-10% of patients.
Excreted Unchanged %
90 (peridoprilat)
Half-Life (Normalesrd) Hours
2.9 (10.9 perindoprilat)/27
Plasma Protein Binding %
20
Volume Of Distribution L/Kg
0.16-0.22
Dose For Normal Renal Function
2 mg q24h
Second Dose
Second Dose: 2-8 mg q24h
Adjustment For Renal Failure Method
D, I
Adjustment For Renal Failure Gfr, Ml/Min >50 [Recommended Level]
2 mg q24h [A]
Adjustment For Renal Failure Gfr, Ml/Min 10-50 [Recommended Level]
2 mg q24-48h[A]
Adjustment For Renal Failure Gfr, Ml/Min <10 [Recommended Level]
2 mg q48h [A]
Supplement For Dialysis [Recommendation Level]: Ihd
IHD: Dose for GFR <10,[B]
Supplement For Dialysis [Recommendation Level]: Pd
PD: Dose for GFR <10, [D]
Supplement For Dialysis [Recommendation Level]: Crrt
CRRT: Dose for GFR 10-50, titrate, [D]
References
Devissaguet JP, Ammoury N, Devissaguet M, Perret L. Pharmacokinetics of perindopril and its metabolites in healthy volunteers. Fundam Clin Pharmacol. 1990; 4: 175-89. [PMID: 2351367] / Gué rin A, Resplandy G, Marchais S, Taillard F, London G. The effect of haemodialysis on the pharmacokinetics of perindoprilat after long-term perindopril. Eur J Clin Pharmacol. 1993; 44: 183-7. [PMID: 8453964] / Hurst M, Jarvis B. Perindopril: an updated review of its use in hypertension. Drugs. 2001; 61: 867-96. [PMID: 11398915] / Sennesael J, Ali A, Sweny P, Vandenburg M, Slovic D, Dratwa M, et al. The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br J Clin Pharmacol. 1992; 33: 93-9. [PMID: 1311597]
Toxicity Notes
Active metabolite is perindoprilat. The clearance of perindoprilat and its metabolites is almost exclusively renal. Approximately 60% of circulating perindopril is bound to plasma proteins, but only 10 to 20% of perindoprilat is bound.