Amlodipine Besylate/Atorvastatin Calcium

Caduet tablets are novel prescription drug that combines amlodipine besylate (AM) with atorvastatin calcium (AT). A spectrofluorimetric and an HPLC-fluorescence detection methods were developed for simultaneous determination of both drugs in tablets. In the spectrofluorimetric method, native fluorescence of AM and AT were measured in methanol at 442 and 369 nm upon excitation at 361 and 274 nm, respectively. The emission spectrum of each drug reveals zero value at the emission wavelength of the other drug, thus allowing their simultaneous determination without interference. In the HPLC method, separation of AM and AT was achieved within 8 minutes on a C18column using acetonitrile:phosphate buffer (0.015 M, pH 3) (45:55, v/v) as the mobile phase. Fluorescence detection was carried out using excitation wavelengths 361 and 274 nm and emission wavelengths 442 and 378 nm for AM and AT, respectively. Excellent linearity was observed. Careful validation proved advantages of the new methods: high sensitivity, accuracy, selectivity and suitability for quality control laboratories.

The efficacy and safety of single-pill amlodipine/atorvastatin for reducing blood pressure (BP), low-density lipoprotein cholesterol (LDLC), and predicted 10-year cardiovascular (CV) risk have been demonstrated in low CV risk countries. The Slovak Trial on Cardiovascular Risk Reduction Following National Guidelines with CaDUET® (amlodipine besylate/atorvastatin calcium; Pfizer, Morrisville, PA, USA; STRONG DUET) study evaluated its clinical utility in Slovakia, one of the highest CV risk regions in Europe.

This was a two-phase study involving 100 outpatient cardiologist and internist departments in Slovakia. Phase 1 assessed BP control and CV risk profiles in adults with treated hypertension, and phase 2 was an open-label, multicenter, observational study. In the phase 2 study, patients with treated but uncontrolled hypertension and three or more coronary heart disease risk factors received single-pill amlodipine/atorvastatin (5/10 or 10/10 mg) for 12 weeks. Major outcomes were the percentage of patients achieving target BP (≤140/90 mmHg) and/or LDL-C (≤3 mmol/L) and reductions in predicted 10-year CV risk.

Of the 4,672 phase 1 patients, 80.8% had uncontrolled hypertension and 61.4% had dyslipidemia. Of the 1,406 phase 2 patients, 90.3% of patients achieved target BP at week 12, 66.3% achieved target LDL-C, and 60.7% achieved both. The mean 10-year CV risk was reduced by 49% (P < 0.0001); treatment was well-tolerated and safe.

Single-pill amlodipine/atorvastatin was associated with significant improvements in BP, LDL-C target attainment, and 10-year CV risk in patients with uncontrolled hypertension in Slovakia. The treatment was well-tolerated and safe. Use of single-pill amlodipine/atorvastatin in high CV-risk countries could lead to significant improvements in CV risk management.