Lisinopril pharmacokinetics

While essentially all ACE inhibitors have a similar mechanism of action and therefore exhibit similar efficacy in the treatment of hypertension and congestive heart failure, these drugs differ slightly in their pharmacokinetic profiles. Enalapril, lisinopril, and quinapril are excreted primarily by the kidney, with minimal liver metabolism, while the other prodrug compounds are metabolized by the liver and renally excreted. Thus, in patients with renal insufficiency, the half-life of renally excreted ACE inhibitors is prolonged. In addition, patients with impaired liver func-... 

Captopril s pharmacokinetic parameters and dosing recommendations are set forth in Table 11-2. Peak concentrations of enalaprilat, the active metabolite of enalapril, occur 3-4 hours after dosing with enalapril. The half-life of enalaprilat is about 11 hours. Typical doses of enalapril are 10-20 mg once or twice daily. Lisinopril has a half-life of 12 hours. Doses of 10-80 mg once daily are effective in most patients. All of the ACE inhibitors except fosinopril and moexipril are eliminated primarily by the kidneys doses of these drugs should be reduced in patients with renal insufficiency. 

No evidence of either a pharmacokinetic or adverse pharmacodynamic interaction was seen in 12 healthy subjects given single doses of nifedipine retard 20 mg and lisinopril 20 mg the effects on blood pressttre were additive. Similarly, there was no pharmacokinetic interaction between single doses of slow-release nifedipine 20 mg and benazepril 10 mg in healthy subjects the effects on blood pressure were additive and the tach-ycardic effect of nifedipine was attenuated by benazepril. The manufacturer of fosinopril notes that the bioavailability of fosinoprilat, the active metabolite, was not altered by nifedipine. - Similarly, the manufacturer of moexipril notes that no clinically important pharmacokinetic interaction occurred with nifedipine in healthy subjects. ... 

Other single-dose studies have shown that food had no statistically significant effect on the pharmacokinetics of lisinopril, or enalapril, and its active metabolite, enalaprilat. Similarly, food had minimal effects on the pharmacokinetics of cilazapril (AUC decreased by only 14%). Food caused small, but statistically significant increases in the time to reach maximum plasma levels of quinapril and its active metabolite. However, as the increase was less than 30 minutes this is not expected to alter the therapeutic effect. Likewise, the manufacturers of spirapril briefly mention in a review that food delayed its absorption by 1 hour, it did not affect the bioavailability of spirapril or spiraprilat, its active metabolite. Other manufacturers state that food had no effect on the absorption of fosinopril 11,12 ramipril, or trandolapril. ... 

A study in 30 healthy subjects found that single and multiple doses of amlodipine 10 mg for 15 days (with or without lisinopril and simvastatin) had no effect on the pharmacokinetics of alcohol 0.8 g/kg nor on subjective psychological performance. Alcohol did not alter the pharmacokinetics of amlodipine. ... 

A brief report states that spirapril does not have a pharmacokinetic interaction with glibenclamide. The manufacturer of exenatide notes that, in a study in hypertensive patients exenatide 10 micrograms twice daily did not alter the steady-state AUC or maximum level of lisinopril 5 to 20 mg daily, but it did delay the time to maximum level by 2 hours. However, exenatide did not alter the blood-pressure lowering effect of lisino-pril. ... 

Subcutaneous exenatide has no important pharmacokinetic interaction with lisinopril, and would therefore not be expected to have a pharmacokinetic interaction with any other ACE inhibitor, although this needs confirmation. 

Vandenbuig MJ, Kelly JG, Wiseman HT, Mannering D, Loi C, Glover DR. The effect of lisinopril on digoxin pharmacokinetics in patients with cor estive heart failure. BrJ Clin Pharmacol 9ZZ) 21,656P-657P. 

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