Fosinopril. pharmacokinetics

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. 

Shionoiri H, Naruse M, Minamisawa K, Ueda S, Himeno H, Hiroto S, Takasaki I. Fosinopril. Clinical pharmacokinetics and clinical potential. Clin Pharmacokinet 1997 32(6) 460-80. 

An aluminium/magnesium hydroxide antacid reduced the bioavailability of captopril by 40%, but this did not seem to be clinically important The bioavailability of fosinopril was reduced by about one-third by Mylanta. An antacid did not affect ramipril pharmacokinetics. 

Propranolol 80 mg three times daily did not affect the pharmacokinetics of a single 20-mg dose of quinapril in 10 healthy subjects. The pharmacokinetics of ramipril 5 mg daily were unaffected by propranolol 40 mg twice daily. Similarly, the manufacturer of fosinopril reports that the bioavailability of fosinoprilat, its active metabolite, was not altered by propranolol. Another study found no significant pharmacokinetic interaction between cilazapril 2.5 mg daily and propranolol 120 mg daily in healthy subjects, but the reductions in blood pressure were about doubled and long-lasting in healthy subjects and in patients with hyperten-... 

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. ... 

Cimetidine did not appear to alter the pharmacokinetics or pharmacological effects of captopril or enalapril, or the pharmacokinetics of fosinopril or quinapril in studies in healthy subjects. The manufacturers of cilazapril say that no clinically significant interaction occurred with H2-receptor antagonists (not specifically named) and the manufacturers of moexipril, " ramipril, and trandolapril say that no important pharmacokinetic interaction occurred with cimetidine. The manufacturers of spirapril briefly note in a review that cimetidine did not alter the plasma concentrations of spirapril or its active metabolite spiraprilat. None of these pairs of drugs appears to interact to a clinically relevant extent, and no special precautions appear to be necessary. 

No important pharmacokinetic or pharmacodynamic interaction has been demonstrated for any ACE inhibitor and coumarin anticoagulant. Contrasting with all this evidence, there is a single, unexplained and isolated case of melaena attributed to an interaction between acenocoumarol and fosinopril. There seems to be no other evidence that fosinopril normally interacts with the oral anticoagulants and so this interaction is unlikely to be of general significance. 

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