Pravastatin, cholestyramine and gemfibrozil in long-term therapy of primary hypercholesterolemia. An open randomized comparative study

In this open controlled clinical trial the lipid-lowering effect, the tolerance and clinical safety of the new hydrophilic HMG-CoA reductase inhibitor pravastatin and cholestyramine were compared in the treatment of 45 patients with primary hypercholesterolaemia over a period of 16 weeks. Following a dietary lead-in of six weeks, patients were randomized at a ratio of 3:2 to receive either pravastatin 10 mg b.i.d. or cholestyramine 8 g b.i.d. The dose of pravastatin was increased to 40 mg per day after eight weeks of treatment and after 16 weeks cholestyramine 8 g b.i.d. was added. Two thirds of the patients in the cholestyramine group were switched to gemfibrocil 900 mg. At the end of the 48 week treatment period the mean reduction rates of total cholesterol, LDL-cholesterol and triglycerides for the pravastatin combination compared to cholestyramine (in brackets values for gemfibrocil) were -30, -35 and -17% versus -17 (-19), -25 (-22) and +27 (-24)%. Pravastatin lead to an increase of the HDL concentration of approximately 8%, gemfibrocil to approximately 13%, whilst cholestyramine alone did not change this lipid fraction. The reduction of total cholesterol and LDL-cholesterol was associated with a decrease in the apolipoprotein B concentration. However, the apolipoprotein AI and AII levels remained unchanged. Due to the absence of clinically relevant side effects and laboratory abnormalities coupled with the excellent compliance in this study, pravastatin proved to be a convincing therapeutic alternative to cholestyramine and gemfibrocil. The combination therapy of pravastatin and cholestyramine offers a potentially highly efficacious and safe therapeutic regimen for the future.     

Clinical studies on acid inhibition by ranitidine given simultaneously with pentagastrin]

In recent years there have been some reports of tolerance occurring in man with the antisecretory effect of H2 antagonists. We, therefore, studied the effect of 300 mg and 600 mg ranitidine (CAS 66357-35-5) daily and increasing i.v. doses of pentagastrin (0.37 microgram/kg, 0.75 microgram/kg, and 1.5 micrograms/kg body weight) on gastric acid output (mmol HCl/30 min) in 9 healthy volunteers. The study design was double-blind, randomized and cross-over. Pentagastrin stimulation was performed on day 1, day 8, and day 16. Increasing i.v. doses of pentagastrin induced an almost identical enhancement of volume secretion, total acid output as well as titratable acidity on the 3 study days. A 16-days treatment period with 300 mg and 600 mg ranitidine led to 80% and 90% inhibition of pentagastrin stimulated acid output. The degree of inhibition evoked by 300 mg and 600 mg ranitidine against pentagastrin was not statistically different during the 16-days treatment period; i.e. no significant tolerance did occur within 16 days. Our data suggest that, in contrast to intragastric acidity measurements, no significant decline of inhibitory effectiveness of ranitidine against i.v. pentagastrin could be observed in healthy male volunteers.     

Gastroduodenal tolerance of tenoxicam versus diclofenac-Na: an endoscopy double-blind controlled study in healthy probands

The gastroduodenal tolerability of tenoxicam vs diclofenac-Na was evaluated in a double-blind, parallel group study in 36 healthy male volunteers. The doses used were 20 mg tenoxicam vs 100 mg diclofenac-Na in a retard formulation daily over a period of 14 days. Gastric tolerability was assessed by using upper endoscopy. Gastroscopy was performed at base-line after the dosing period of 14 days and again after a follow-up period of 14 days without any treatment. The mucosal lesions were scored using modified Lanza criteria. In comparison to diclofenac-Na, tenoxicam was significantly better tolerated after a 14-day dosing period (mean gastric score: tenoxicam: 1.3 +/- 0.7; diclofenac-Na: 2.2 +/- 1.1 p = 0.0143). Both treatment groups had comparable scores at base-line and post-study assessments. Tenoxicam and diclofenac-Na were generally well tolerated. Only two volunteers reported intermittent lack of appetite, heartburn, and a feeling of pressure in the stomach. In summary, tenoxicam given as a 20 mg single oral morning dose over a 14-day period was significantly better tolerated than diclofenac 100 mg with regard to gastroduodenal mucosal damage.