Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension.

摘要: Trandolapril/verapamil sustained release (SR) [Tarka®] is an oral, fixed-dose combination of the ACE inhibitor trandolapril and SR formulation phenylalkylamine calcium channel antagonist verapamil. It indicated for treatment hypertension in patients who require more than one agent to achieve blood pressure (BP) targets. In large, randomised, multicentre INVEST (INternational VErapamil SR/trandolapril STudy), a verapamil SR-based strategy that included most was as effective atenolol-based reducing risk primary outcome (first occurrence death [all-cause], nonfatal myocardial infarction [MI] or stroke) with coronary artery disease (CAD) well tolerated. generally at controlling either component monotherapy, number other therapies. The tolerated monotherapy least monotherapy. hypertensive type 2 diabetes mellitus BENEDICT (BErgamo NEphrologic DIabetes Complications Trial), trandolapril/verapamil prolonged time onset persistent microalbuminuria compared placebo, did Thus, option essential requiring BP targets, including those compelling indications, such CAD diabetes. Trandolapril, prodrug active metabolite trandolaprilat, reduces vasopressor activity aldosterone provides negative feedback renin secretion by inhibiting conversion angiotensin I II. causes dilation peripheral vasculature, thus decrease BP, influx ions through L-type channels. improves left ventricular (LV) wall structure function preserves LV heart failure. Cardiac events are less common failure following acute MI. Peak plasma concentrations (Cmax) trandolaprilat achieved 0.5–1.5 3–12 hours after single oral dose 2mg healthy volunteers. Cmax steady state double dose. Trandolapril converted hepatic metabolism. absolute bioavailability parent drug ≈10% 70%; both highly protein-bound. respective terminal elimination half-lives (t1/2β) 6 10 hours, majority excreted faeces. Verapamil ≈5 hours. Due extensive first-pass metabolism liver, has 10–35%. bound proteins. desmethyl species, norverapamil. t1/2β 8 repeated administration, urine metabolites. There no clinically relevant pharmacokinetic interactions between when two agents coadministered. A which also received preventing MI [9.9% vs 10.2%; mean follow-up 2.7 years] large (n = 22 576), INVEST. Similar proportions receiving US Joint National Committee (JNC) VI targets (current consensus guidelines conducted) control 100), 1mg/180mg, 2mg/180mg, 2mg/240mg 4mg/240mg per day corresponding dosages sitting from baseline adult hypertension. 1mg/180mg 2mg/180mg were 24-hour ambulatory systolic diastolic therapies (metoprolol/hydrochlorothiazide, atenolol/chlortalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide). unresponsive administered special patient populations, Black elderly Compared double-blind, BENEDICT, clinical trials had tolerability profile similar individual components class drug. incidence adverse (9–46%) withdrawal rates due (2.0–11.7%) comparator arms. INVEST, strategies equally occurring frequently placebo cough, first-degree atrioventricular block constipation. Gastrointestinal tract and/or constipation likely studies.