Bioavailability of amlodipine besylate/atorvastatin calcium combination tablet.

The bioequivalence of combination tablets containing amlodipine besylate/atorvastatin calcium with coadministered matching doses of amlodipine besylate and atorvastatin calcium tablets was investigated in randomized, 2-way crossover studies in healthy volunteers (N = 126). Subjects received a single dose of the amlodipine/atorvastatin tablet or coadministered matching doses of amlodipine and atorvastatin at the highest (10/80 mg; n = 62) and lowest (5/10 mg; n = 64) dose strengths. Atorvastatin geometric mean ratios for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) for the highest and lowest dose strengths were 94.1 and 98.8, and 104.5 and 103.8, respectively. Amlodipine geometric mean ratios for C(max) and AUC for the highest and lowest dose strengths were 100.8 and 103.4, and 100 and 102.7, respectively. The 90% confidence intervals for all comparisons were within 80% to 125%, demonstrating bioequivalence for amlodipine and atorvastatin at both dose strengths. Use of amlodipine/atorvastatin combination tablets may provide a more integrated approach to treatment of cardiovascular risk.

The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients.

BACKGROUND: Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. METHODS: Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. RESULTS: Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17% higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96% in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. CONCLUSION: The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension.

Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediate-release glipizide in patients with type II diabetes mellitus.

This study was designed to compare the pharmacokinetic and short-term pharmacodynamic profile of extended-release glipizide GITS (Glucotrol XL) given in a dosage of 20 mg once daily with that of immediate-release glipizide (Glucotrol) 10mg twice daily in patients with type II diabetes mellitus. In an open-label, randomized, two-way crossover study, each glipizide formulation was administered for 5 days. Serial blood samples were drawn at baseline and on the 5th day of each treatment phase for measurement of glipizide, glucose, insulin, and C-peptide concentrations. At steady state, the mean Cmax after immediate-release glipizide was significantly greater than after glipizide GITS, and the tmax was considerably shorter. Although the mean Cmin with glipizide GITS was about 80% higher than with immediate-release glipizide, the mean AUC0-24 was significantly lower. Despite the lower plasma concentrations with glipizide GITS in this short-term study, the two formulations had similar effects on serum concentrations of glucose, insulin, and C-peptide. The absence of a pronounced peak plasma concentration with the GITS formulation might confer advantages in terms of maintaining clinical effectiveness and reducing the potential to cause adverse effects.