A multicenter, randomized, double-blind comparison of roxatidine with ranitidine in the treatment of patients with uncomplicated benign gastric ulcer disease. The Multicenter Roxatidine Cooperative Study Group.

Roxatidine (150 mg, 312 patients) was compared with ranitidine (300 mg, 308 patients) in a randomized, double-blind, parallel-group, 6-week therapeutic study for the treatment of patients with uncomplicated, benign gastric ulcer disease. The study end points (verified by using endoscopy results) were fully healed ulcers at 4 or 6 weeks. The results of roxatidine therapy were comparable to those of ranitidine therapy: healing rates of 52% and 54% at week 4 and 77% and 76% at week 6 were recorded for roxatidine and ranitidine, respectively. The drugs produced comparable reductions in ulcer diameters and decreases in abdominal pain. Adverse events associated with both roxatidine (27%) and ranitidine (28%) were headache, diarrhea, and dizziness; rash was associated in 6 of 8 cases and in only 1 case with roxatidine. In this trial, roxatidine 150 mg once daily was as efficacious and safe as ranitidine 300 mg once daily for treatment of patients with uncomplicated, benign gastric ulcer disease.

A multicenter, double-blind, randomized, placebo-controlled comparison of nocturnal roxatidine in the treatment of active duodenal ulcer disease. Multicenter Roxatidine Cooperative Study Group.

This multicenter randomized, double-blind, 4-wk study compared the new H2-receptor antagonistic roxatidine (R) to placebo (P) for treatment of endoscopically diagnosed active duodenal ulcer disease. Subjects were evaluated after 2 and 4 wk of treatment. Those whose ulcer was unhealed at 2 wk received 2 more weeks of treatment before final evaluation. Ulcer healing (endoscopically determined) with roxatidine was more effective than placebo at both wk 0-2 (R = 33.9%, P = 21.9%, p = 0.018) and wk 2-4 (R = 68.2%, P = 29.7%, p less than 0.001), with an overall 4-wk effectiveness of 78.9% compared to 44.8% (p less than 0.001). At the end of treatment, average maximum ulcer diameter diminished 83% in R and 50% in P (p less than 0.001). Roxatidine was also more effective than placebo in decreasing abdominal pain (p less than 0.001), decreasing the number of antacid tablets taken for pain relief (p less than 0.001), improving dyspeptic symptoms (p less than 0.001), and permitting return to a normal routine for subjects with previous illness-imposed restrictions on work and/or other daily activities. The profile of laboratory values and adverse experiences demonstrated roxatidine to be safe and well-tolerated. The efficacy of roxatidine as evaluated by the healing rate of duodenal ulcer and reduction in abdominal pain emphasize its value as an addition to the family of H2-receptor antagonists.

Dose-response effects of pentoxifylline on erythrocyte filterability: clinical and animal model studies.

Ten patients with chronic occlusive arteriosclerosis received single oral doses of 100, 200, 400, 800, and 1200 mg pentoxifylline in a single-blind, placebo-controlled study. Blood samples were drawn at baseline and at 2 hour intervals for 6 hours. Drug and metabolite levels, as well as red cell filterability (deformability), were determined on all blood samples. Statistically significant dose-response increases of red cell filterability were found 4 and 6 hours after oral medication with the dosages of 200 to 1200 mg pentoxifylline. These changes were proportional to the plasma levels of pentoxifylline and metabolites 1 and 5 of this agent. Attempts were made to develop a suitable animal-screening method for agents with similar activity and to determine whether red blood cells in the absence of disease-related abnormalities may respond to this type of therapy. Five healthy Macaca arctoides monkeys were given 24 mg/kg pentoxifylline intravenously, and measurable but lesser increases in red cell deformability were recorded than in the patients.

Efficacy and safety of pentoxifylline in geriatric patients with intermittent claudication.

The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.

Pentoxifylline treatment of moderate to severe chronic occlusive arterial disease.

A pilot study of the effects of pentoxifylline in 19 patients with moderate to severe chronic occlusive arterial disease (COAD) is described. The severity of disease was assessed by the degree of limitation in the walking distance on the flat surface (less than 100 m), the absence of peripheral pulses on palpation, the diminished Doppler tibial/brachial pressure (the ischemic index) at rest, and by contrast arteriography, when available. After a 2-week washout phase, all subjects received pentoxifylline (1200 mg/day) in an open-label manner for a total of 12 weeks. Twelve of the nineteen patients showed a definite increase in exercise tolerance by the end of the study, with a concomitant reduction in ischemic symptoms. All except 3 patients felt they had derived benefit from the medication. In contrast to the clear improvements in walking distance and symptoms, only small effects on noninvasive vascular laboratory measurements were noted. Platelet aggregation, induced by ADP, epinephrine, and collagen, gradually decreased over the study period. Pentoxifylline appears to be useful in the medical management of patients with moderate to severe chronic occlusive arterial disease; future controlled trials in such patients are now justified.

Real-time B-mode ultrasonography of the femoral arteries: comparison to contrast arteriography.

Forty-five patients with symptomatic peripheral vascular disease were studied with a high-resolution, real-time B-mode echo imaging system for visualization of the femoral arteries. Common femoral and superficial femoral arteries were visualized in over 88 per cent of cases, whereas the profunda femoris artery was demonstrated in only about one-third of cases. Stenotic lesions (+ or - 20% of arteriographic assessment) were identified in two-thirds of cases. Prostheses and grafts in the proximal and medial cases. Prostheses and grafts in the proximal and medial thigh were well visualized. Anatomic information provided by B-mode imaging will complement functional assessments of lower extremity vascular insufficiency.

Kinetics of single doses of fenbufen in patients with renal insufficiency.

Fenbufen (gamma-oxo[1,1'-biphenyl]-4-butanoic acid) is a nonsteroidal anti-inflammatory analgesic that is metabolized to four major metabolites: gamma-hydroxy [1,1'-biphenyl]-4-butanoic acid (II), [1,1'-biphenyl]-4-acetic acid (III), 4'hydroxy [1,1'-biphenyl]-4-acetic acid (IV), and gamma, 4'-dihydroxy [1, 1'-biphenyl]-4-butanoic acid (V). Fenbufen and metabolites II and III circulate to plasma and are pharmacologically active; metabolites IV and V are normally excreted in urine. Single 800-mg doses of fenbufen were safely administered to 10 healthy subjects and to 16 patients with varying degrees of renal insufficiency. Drug and metabolite concentrations in serum and urine were determined at intervals for 3 days. It was found that renal impairment altered the metabolic pattern of fenbufen. Although t1/2 beta was the same for fenbufen and II, their plasma levels fell. No change was found in the plasma levels of III. There was evidence of moderate cumulation in plasma of the two more polar urinary metabolites (IV, V) corresponding to the degree of renal insufficiency. The total of all five compounds excreted into the urine was diminished. To account for this, either biliary and gastrointestinal excretion increased or there may have been further hepatic biotransformation of the metabolites.

Comparison of pulsed Doppler and real-time B-mode echo arteriography for noninvasive imaging of the extracranial carotid arteries.

Accuracy and clinical applications of noninvasive imaging of the extracranial carotid arteries were compared using pulsed Doppler and real-time B-mode ultrasonography. During the period December, 1977, to February, 1979, 530 ultrasonograms (265 patients) were performed. Angiographic correlations were available in 90 patients (172 arteries) using the pulsed Doppler technique, and both techniques were employed in 43 patients (84 arteries). Greatest accuracy with pulsed Doppler ultrasonography occurred in confirmation of normal vasculature (73%) and diagnosis of occluded internal carotid arteries (96%). Estimation of the percentage of stenosis was less accurate; however, this determination could be made somewhat more accurately by B-mode ultrasonography. Incidence of false positive and negative results for the pulsed Doppler technique was 11% and 14%, respectively, whereas for the corresponding incidence for B-mode imaging it was 11% and 59%. The higher incidence of false negative results with the B-mode technique related to its inaccuracy in diagnosis of occlusion (18%). Current clinical applications of carotid ultrasonography include confirmation of normalcy and diagnosis of occlusion, visualization of atheroslerotic plaques with characterization of their size and ultrasonic morphology, and an anticipated reduction in the requirements for contrast arteriography in selected patients.

A clinical safety trial of stroma-free hemoglobin.

A stroma-free hemoglobin (SFH) solution was prepared which was sterile, pyrogen free, and contained only 1.2% of the stromal lipid present in unpurified hemolysate, 250 ml of which was administered slowly intravenously to 8 healthy men. Two control subjects received 250 ml of serum albumin. The SFH infusions were generally well tolerated by 7 of the 8 men. One subject developed abdominal pain and costovertebral angle tenderness after infusion, which disappeared within 48 hr. Bradycardia and a mild increase in blood pressure was present during ths SFH infusions and for 4 to 5 hr thereafter. A decrease in urine output and endogenous creatinine clearance appeared during the SFH infusions and for 2 to 4 hr after infusion. A mild prolongation of the activated partial thromboplastin time developed immediately after infusion. Gross hemoglobinuria appeared as expected during the SFH infusions and completely disappeared by 6 to 10 hr after infusion. All the cardiovascular, renal, and clotting changes were present for only a few hours after the SFH infusion, during the hemoglobinemia (free Hb in plasma). At 24 hr and 7 days after infusion all measurements were normal, and 6 mo follow-up showed no abnormalities or hepatitis.