Worldwide clinical experience with sultamicillin.

Sultamicillin at an adult dose of 375-750 mg twice daily or a pediatric dose of 50 mg/kg/d provides effective outpatient/office therapy for community-acquired infections of the upper and lower respiratory tract, urinary tract, and skin/soft tissue structures. Given the incidence of Haemophilus influenzae and Branhamella catarrhalis in otitis media and the frequent occurrence of beta-lactamase-producing strains, it is particularly appropriate for the therapy of otitis media in infants and children. The increasing prevalence of beta-lactamase-producing pathogens in these infections, coupled with the fact that diagnostic bacteriology is often not available or practical in office practice, suggests that the broad use of sultamicillin might be desirable. Several factors support such usage: 1) the superiority of sultamicillin compared with the ampicillin commercial dosage form as a delivery system for ampicillin; 2) the possible occurrence at the infection site of beta-lactamase-producing organisms, not themselves pathogens, which nevertheless impair the activity of the beta-lactam antibiotic against sensitive pathogens; 3) the complementary binding of penicillin-binding proteins by ampicillin and sulbactam in ampicillin-sensitive organisms; 4) the lack of resistance development following repeated exposure of strains sensitive to sulbactam/ampicillin suggested by in vitro studies; and 5) the inability of sulbactam to induce beta-lactamase production. In addition to broad use in community-acquired infections, oral therapy with sultamicillin should also provide convenient outpatient follow-up for initial parenteral sulbactam/ampicillin therapy. Extensive testing of various laboratory parameters has revealed no evidence of systemic toxicity with sultamicillin. The only significant side effect of sultamicillin is diarrhea/loose stools, which, although a frequent complaint in some studies, is of mild to moderate severity and results in a low discontinuation rate.

Clinical experience with sorbinil--an aldose reductase inhibitor.

A considerable volume of animal pharmacologic data support the view that increased flux through the polyol pathway provides a unifying hypothesis for the major complications of diabetes. An extensive clinical program has been established to verify the extrapolation of the animal pharmacologic findings to man. Clinical data accumulated to date confirm the biochemical and electrophysiologic effects, and encouraging evidence of a drug effect in diabetic neuropathy and retinopathy has already been observed. In the large, controlled safety data base already available, the long-term clinical use of sorbinil is devoid of significant adverse effects in terms of both subjective side effects and laboratory parameters. The only clinically important adverse reaction reported to date has been a hypersensitivity reaction in the early weeks of therapy, which is similar to that seen with other hydantoins.

Aldose reductase inhibitors in clinical practice. Preliminary studies on diabetic neuropathy and retinopathy.

Extensive animal data now exist to indicate potential benefit of sorbinil in the treatment of the major complications of diabetes mellitus. A clinical programme has been constructed to explore this therapeutic potential and encouraging evidence of drug effect has already been observed in patients with neuropathy and retinopathy. Two small preliminary studies in patients with painful neuropathy have shown that clinically significant reduction of pain was more frequently achieved with sorbinil than with placebo. A 6-month study of patients with retinopathy, using vitreous fluorophotometry as the criterion of retinal damage, showed significant (p = 0.03) benefit for the sorbinil group compared with the placebo group. Drug evaluation in these areas is complex and difficult but it is anticipated that the accumulation of additional data will further substantiate the efficacy suggested by these early findings. The only clinically important adverse effect of sorbinil is the hypersensitivity reaction. This usually occurs during the initial weeks of therapy and is similar to that seen with phenytoin. The long term use of sorbinil is without significant adverse effects.

The clinical evaluation of prazosin, a new antihypertensive agent.

The hemodynamic and therapeutic profiles of prazosin have been delineated in a comprehensive clinical program involving more than 1,000 patients. Efficacy was established in double-blind placebo-controlled studies and open, noncomparative long-term studies and comparisons with standard antihypertensive agents. The efficacy and safety of prazosin make it particularly suitable for initiation and maintenance of long-term outpatient therapy for hypertension.