Enalapril dosing

A 45-year-old man who had taken enalapril (dose not reported) for more than 2 years presented with hepatitis with negative viral serology (8). Biopsy showed necrosis and cholestasis. He recovered fuUy after drug withdrawal (timing not reported). 

B. While on cefotetan, MN will have to increase his enalapril dose. 

Enalapril 2.5 to 5 mg initially target dose 10 mg twice daily. 

All 10 ACE inhibitors available in the United States can be dosed once daily for hypertension except captopril, which is usually dosed two or three times daily. The absorption of captopril (but not enalapril or lisinopril) is reduced by 30% to 40% when given with food. 

Some optically active compounds have been studied [54], The benzazepinone diacid (CGS 12831, 27) was found to have the best in vitro inhibitor potency in a series of lactam compounds, but it showed only marginal biological activity following oral administration, presumably because of poor absorption. The corresponding monoethyl ester (CGS 14824A, 28) was much more potent in vivo [54, 56]. This compound (28) was found to produce dose-dependent antihypertensive effects in conscious normotensive and spontaneous hypertensive rats, generally similar to those produced by enalapril. Evaluation of (28) in healthy volunteers [57, 58] shows that it is an effective,... 

Patients taking diuretics - Discontinue the diuretic, if possible, for 2 to 3 days before beginning therapy with enalapril to reduce the likelihood of hypotension. If the diuretic cannot be discontinued, use an initial dose of 2.5 mg under medical supervision for at least 2 hours and until BP has stabilized for at least an additional hour. 

For conversion from IV to oral therapy, the recommended initial dose of enalapril maleate tablets for patients who have responded to 0.625 mg enalaprilat every 6 hours is 2.5 mg once a day with subsequent dosage adjustment as needed. 

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. 

Usual maintenance range is 20 mg/d to 40 mg/d in a single dose Enalapril... 

Enalapril may cause anemia. It has been used successfully in low doses for posttransplant polycythemia. ACE inhibitors may precipitate renal failure in patients with renal transplant artery stenosis. A rapid rise in serum creatinine after initiation of ACE inhibitor therapy may indicate renal transplant artery stenosis. 

A 63-year-old man reduced his dietary sodium intake to combat fluid retention and was taking furosemide 40 mg/ day, spironolactone 50 mg/day, and enalapril 2.5 mg/day (26). He then took amiodarone 800 mg/day for 7 days and his serum sodium concentration fell to 119 mmol/1 his plasma vasopressin concentration was raised at 2.6 pmol/1. The dose of amiodarone was reduced to 100 mg/day, with fluid restriction his sodium rose to 130 mmol/1 and his vasopressin fell to 1.4 pmol/1. 

Portoles, A., Terleira, A., Almeida, S., et al. Bioequivalence study of two formulations of enalapril, at a single oral dose of 20 mg (tablets) A randomized, two-way, open-label, crossover study in healthy volunteers. Curr. Ther Res. 65(1) 34—46, 2004. 

Peak concentrations of enalaprilat, the active metabolite, 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. 

The phase I clinical testing of enalapril began in 1980 in a study in which its efficacy to inhibit intravenously administered angiotensin I was determined. Oral doses as low as 2.5 mg produced a substantial decrease in ACE, activity and lowering was evident even 21-24 hours after the drug was given (129). Phase II and phase III trials began in 1981, and the first approval to use enalapril in hypertension came in 1984 and in heart failure in 1986. 

With the data included in the overview of Garg et al. (316), it is possible to calculate that 18 patients need to be treated for 90 days to avoid one death or one hospitalization for congestive heart failure (95% confidence interval [Cl] 16-23). This meta-analysis includes 32 trials with the ACE inhibitors captopril, enalapril, lisinopril, quinapril, ramipril, and perindopril. It is likely that high doses (for instance, lisinopril 35 mg daily) are more effective than low doses (lisinopril 5 mg daily) (302). Treating 30 patients for 4 years with a high dose of lisinopril (95% Cl 16-509) will avoid one hospitalization for cardiovascular reasons or one death in comparison with a low dose, without increasing the number of adverse effects requiring withdrawal from treatment. 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

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