The pharmacokinetics of acebutolol have been studied in eight healthy male volunteers following the oral administration of acebutolol hydrochloride ('Sectral', May & Baker) as a single dose (400 mg), and during and after repeated oral dosing (400 mg, b.d. for 56 days). Following single dose administration, considerable inter-subject variation in plasma levels of parent drug and the major metabolite, diacetolol, was evident. Acebutolol appeared to be eliminated from plasma in a bi-phasic manner, and this was confirmed from urinary excretion rate data. Mean initial and terminal half-lives of about 2 and 11 h, respectively, were determined. Plasma levels of diacetolol were greater than those of parent drug from 3 to 4 h following dose administration. Total urinary excretion of diacetolol was generally greater than that of acebutolol. During repeated dosing, steady-state plasma levels of acebutolol and diacetolol were achieved in 6 volunteers. Acebutolol did not appear to stimulate or inhibit its metabolism.
SummarySix 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 400mg 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.
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