[Investigations on the pharmacokinetics of apalcillin in man]

Plasma levels and urinary excretion was studied after i.v. bolus of 1000 mg (2S,5R,6R)-6-[(R)-2-(4-hydroxy-1, 5-naphthyridine-3-carboxamido)-phenylacetamido]-3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (apalcillin, PC-904) and after long-term infusion of 3000 mg apalcillin in volunteers of both sexes. For measuring the concentrations a cylinder agar diffusion test was used. The plasma levels decreased from 150 microgram/ml 2 min after injection to 100 microgram/ml 15 min p.a. and to 37 microgram/ml after 90 min. For the terminal half-life of elimination from plasma a value of 1.0 was calculated. After termination of the long-term infusion concentrations of 70-80 microgram/ml were found in plasma. In this case a terminal half-life of 1.5 h was calculated. Due to the fast half-life of elimination no cumulation will occur in the case of repetitive dosing. This suggestion is supported by the finding, that the mean transit time of 1.4 h is very short. On the other hand the substance is distributed so rapidly that therapeutic levels are reached 30 min after infusion. Using data from literature, a proportionality between dose and area under the plasma curve could be demonstrated in the range 1000-3000 mg apalcillin. Our results show that about 20% of the dose administered is found in urine. 10 h after application the urinary excretion is finished. No side effects were observed during the acute assays.