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Studies on pivampicillin hydrochloride and ampicillin trihydrate, administered in capsules to healthy volunteers, indicated that pivampicillin was absorbed more efficiently from the gastrointestinal tract than ampicillin. Average peak concentrations of ampicillin in the serum after doses equimolar to 250 mg of ampicillin were 6.8 μg/ml at 56 min with pivampicillin and 1.96 μg/ml at 1 h 24 min with ampicillin. The maximal concentration after pivampicillin treatment was also higher than that recorded when twice the equimolar dose of ampicillin, which averaged 3.2 μg/ml at 1 h 42 min, was used. The urinary excretion of ampicillin, expressed as a percentage of the administered dose, averaged 67 to 73 and 25 to 29% after administration of pivampicillin and ampicillin, respectively. The bioavailability of ampicillin, taken as the area under the serum curve, obtained with pivampicillin at a 250-mg ampicillin dose level was superior to that obtained with a 500-mg dose of ampicillin. Comparison of a suspension intended for children, containing the pivampicillin free base with a suspension of ampicillin trihydrate, emphasized the difference recorded for the capsule preparations. Administration of pivampicillin with a meal rich in fat and protein had no depressant effect on the absorption. Concurrent administration of probenecid caused higher and prolonged concentrations of ampicillin in the serum.

A common structural feature of all penicillins used in medicine is the presence of an acylamido group in the 6s-position of penicillanic acid, (cf. fig.l) and it has been generally assumed that this grouping is a prerequisite for antibacterial activity of s-lactam antibiotics.

A GLC determination of bumetanide (3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid), a potent „high ceiling” diuretic, was developed using flash-heater methylation. A mixture of tetramethylammonium hydroxide and trimethylanilinium hydroxide was advantageously used as the methylation reagent. The flash-heater methylation product proved to be methyl 3-(N-n-butylanilino)-5-dimethylsulfamyl-4-methoxybenzoate by spectroscopic comparison with authentic material achieved by a corresponding gram scale model experiment. The probable sequence of reactions involving methylation under simultaneous Smiles rearrangement is outlined. The GLC determination was found to be accurate at concentrations as low as 0.1 mcg./ml. human urine. In six healthy volunteers, the urinary recovery of bumetanide, the urinary excretion of sodium, potassium, and chloride ions, and the urine volume were determined after oral administration of 0.5 and 1 mg. of the drug. A parallelism between bumetanide excretion and saluretic action over the total period of response is shown.

The effect of bendroflumethiazide on the teeth of rats on a carious diet was examined and compared to that of sodium fluoride to determine whether release of fluoride takes place from the trifluoromethyl group of the substance. No detectable fluoride was released.

The preparation of the acetoxymethyl and pivaloyloxymethyl esters of cephaloglycin is described. These esters are well absorbed from the gastrointestinal tract and after the absorption are cleaved enzymatically with the liberation of cephaloglycin. As a result high blood- and tissue-levels of the latter are attained.

FROM the fermentation broth of a strain of Fusidium a hitherto unrecorded antibiotic, for which the name ‘fusidic acid’ is proposed, has been isolated.