Plasma captopril concentrations

ACE INHIBITORS PROBENECID t plasma concentrations of captopril and enalapril uncertain clinical significance Renal excretion of captopril and enalapril l by probenecid Monitor BP closely... 

ACE INHIBITORS DIGOXIN t plasma concentrations of digoxin when captopril is co-administered in the presence of heart failure (class II or more severe) or renal insufficiency. No other ACE inhibitors seem to interact in the same way Uncertain postulated to be due to 1 renal excretion of digoxin Monitor digoxin levels watch for digoxin toxicity... 

Muller H-M, Overlack A, Heck I, Kolloch R, Stumpe KO. The influence of food intake on pharmacod3fnamics and plasma concentration of captopril. JHypertens (1985) 3 (Suppl 2), S135-S136. 

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. 

Fig. 5 Correlation over time of systolic blood pressure ( ) with plasma unchanged captopril concentration (H) after sublingual (A) and peroral (B) administration of 25 mg of captopril. (From Ref 1)...

The determination of plasma renin responsiveness, however, is not sufficient to diagnose primary aldosteronism because suppressed PRA also occurs in about 25% of patients with essential hypertension. Primary aldosteronism can be differentiated from other hypermineralocorticoid states on the basis of inappropriate secretion of aldosterone. The demonstration of an elevated concentration of aldosterone in blood or urine in a patient with an unequivocally suppressed PRA concentration (a plasma aldosterone/ plasma PRA ratio >50) is presumptive evidence of primary aldosteronism. Because hypokalemia has a suppressive effect on aldosterone secretion, the potassium deficit should be replaced before aldosterone measurements are done. To establish aldosterone autonomy, the clinician may attempt to suppress aldosterone production with rapid volume expansion (see Box 51-10), with a potent mineralocorticoid (see Box 51-11), or as mentioned with captopril. Failure... 

Routine laboratory tests may help to identify secondary hypertension. Baseline hypokalemia may suggest mineralocorticoid-induced hypertension. Protein, blood cells, and casts in the urine may indicate renovascular disease. Some laboratory tests are used specifically to diagnose secondary hypertension. These include plasma norepinephrine and urinary metanephrine concentrations for pheochromocytoma, plasma and urinary aldosterone concentrations for primary aldosteronism, and plasma renin activity, captopril stimulation test, renal vein renins, and renal artery angiography for renovascular disease. 

Captopril (capoten) Captopiil is a potent ACE inhibitor (K -1.7 nM). Given orally, captopril is absorbed rapidly and has a bioavailabihty of -75%. Peak concentrations in plasma occur within an hour, and the drug is cleared with a tj of 2 hours. Most of the drug is eliminated in urine, 40-50% as captopril and the rest as captopril disulfide dimers and captopril-cysteine disulfide. The oral dose of captopril ranges from 6.25 to 150 mg two to three times daily, with 6.25 mg three times daily or 25 mg twice daily being appropriate for the initiation of therapy for heart failure or hypertension, respectively. Most patients should not receive daily doses in excess of 150 mg. Since food reduces the oral bioavailabiUty of captopril by 25-30%, the drug should be given 1 hour before meals. 

Responses, in terms of the increases in systolic (SBP) and diastolic (DBP) blood pressures, to test peptide and bradykinin are determined. After ganglion blockade with pentolinium (group GB) without or with added captopril (group GB+Cap), heart rate and plasma adrenaline and noradrenaline concentrations are determined. In some cases, the rats are not subjected to ganglion blockade and served as controls for animals in the GB group (control group). 

Someya, N., Kodama, K. and Tanaka, K. (1985). Effect of captopril on plasma prostacyclin concentration in essential hypertensive patients. Prostagi Leuk. Med., 20, 187-195... 

---