Preliminary study of the disposition in man of acebutolol and its metabolite, diacetolol, using a new stereoselective hplc method.

A new stereospecific hplc method that is capable of simultaneously quantitating the S-(-)- and R-(+)-enantiomers of acebutolol and its major metabolite, diacetolol, in plasma and urine, is described. When applied to the assay of biological fluids collected during single and chronic oral dosing with acebutolol (Sectral), this procedure failed to reveal any important stereoselectivity in the disposition of either acebutolol or diacetolol in man. This may occur because acebutolol is metabolized by hydrolysis and N-acetylation, whereas the other beta-blockers which exhibit some degree of stereoselective disposition (e.g. metoprolol and propranolol) are primarily metabolized by oxidation.

The penetration of trimethoprim and sulphamethoxazole into synovial fluid.

A group of six patients with non-infected synovial effusions requiring diagnostic or therapeutic aspiration, were given a short oral course of 'Septrin' (two tablets bd for two doses, each tablet containing 80 mg of trimethoprim plus 400 mg of sulphamethoxazole). Serum and synovial fluid (SF) were sampled frequently following antibiotic administration. It was found that concentrations of trimethoprim in SF approached serum levels after a short lag time (about 3 h) and thereafter approximated to the serum levels, whereas sulphamethoxazole did not as readily penetrate into SF. With the regimens used MIC levels for trimethoprim were achieved in SF, which suggests that this drug could be usefully prescribed in normal doses for the treatment of septic arthritis due to bacterial infection.

Acebutolol and coronary artery surgery. Plasma levels following oral pre-operative treatment.

Plasma levels of acebutolol and its major human metabolite, diacetolol, were determined before, during and after aortocoronary bypass grafting in 10 patients who had received a chronic oral regimen of acebutolol 200 mg t.d.s. for at least 6 days before surgery, a 200 mg dose with the premedication and 5-10 mg intravenously immediately before intubation. It was found that this regimen produced beta-adrenoceptor antagonist levels which were within the range in which attenuation of hypertension and tachydysrhythmia occurs. These effective plasma levels were sustained throughout surgery and persisted into the early recovery period.

The penetration of metronidazole into synovial fluid.

Six patients with non-infected synovial effusions, associated either with inflammatory or degenerative arthropathy and requiring diagnostic or therapeutic aspiration, were given a short course of 400 mg metronidazole (Flagyl) 8-hourly for 3 doses. Serum and synovial fluid (SF) were sampled frequently during this time, and assayed for metronidazole by a specific high pressure liquid-chromatographic method. It was found that concentrations of metronidazole in SF reached those in serum after a short time-lag, and thereafter approximated to the serum concentration. With this regimen, metronidazole concentrations were readily achieved in synovial fluid, above the minimum inhibitory concentrations for most susceptible anaerobes. These results indicate that the drug freely enters the synovial fluid and suggests that metronidazole would prove effective in the treatment of septic arthritis due to anaerobic bacteria.

Serum, saliva, and sputum levels of metronidazole in acute exacerbations of chronic bronchitis.

We have evaluated the absorption and the penetration of metronidazole into the bronchial secretions and saliva in acute infective exacerbations of chronic bronchitis. Seventeen patients were given 400 mg orally three times daily for seven days and "steady state" levels were measured in serum, saliva, and sputum on the last day of treatment. Mean levels in the three biological fluids were not significantly different. Higher metronidazole levels in sputum tended to occur in patients with higher serum levels. In all but one patient, levels in serum and saliva were well within the therapeutic range. We conclude that this oral regimen results in therapeutic tissue levels in acute exacerbations of chronic bronchitis.