Captopril half-life

In conclusion, CPD represents a prodrug of captopril which seems to lengthen the pharmacokinetic half-life and extend the duration of action of captopril in humans. 

The onset of action following oral administration of captopril is about 15 minutes, with peak blood levels achieved in 30 to 60 minutes. Its apparent biological half-life is approximately 2 hours, with its antihypertensive effects observed for 6 to 10 hours. The kidneys appear to play a major role in the inactivation of captopril. 

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. 

The half-life of captopril is short (<3 hours). A drug with a short half-life requires more frequent dosing to maintain an effective concentration in the body. This can result in inadvertently missed doses. More important than the short half-life, some patients taking captopril report rashes and a lack of taste sensation (dysgeusia). 

Enalaprilat proved to be significantly more active than captopril, although its oral bioavailability was low. The monoethyl-ester pro-drug, enalapril, was used to solve this problem to provide an AC E-inhibitor with a longer duration of action because of the longer plasma half-life of enalaprilat (11 h). Enalapril has one further advantage over captopril, in that its oral bioavailability is not reduced by the presence of food. 

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). 

In a pharmacokinetic study, 19 healthy subjects were given moracizine 250 mg or captopril 50 mg, both every 8 hours, either alone or together, for 22 doses. When taken together the pharmacokineties of the moracizine and total captopril remained unchanged, but the maximum blood levels of the free captopril and its AUC decreased by 32% and 14%, respectively. The half-life of the free captopril was reduced by 44%. These modest changes are unlikely to be clinically relevant. 

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