Serum and urinary concentrations of cyclacillin in humans

Cyclacillin is a semisynthetic penicillin produced from the penicillin nucleus (6-aminopenicillanic acid) by acylation with 1-aminohexanecarboxylic acid. The absorption and excretion characteristics of cyclacillin were defined in one completely randomized and three three-way crossover experiments. Mean peak serum cyclacillin levels appeared earlier and were fivefold higher than those obtained with equal doses of ampicillin. High serum cyclacillin concentrations were reached at 0.5 h and by 2 h were lower than ampicillin. Serum ampicillin concentrations peaked at 1.5 h, remaining slightly higher than those for cyclacillin for the next 4.5 h. The mean area for the cyclacillin curve was significantly superior to either of the ampicillin formulations. Mean serum concentrations of cyclacillin exhibited a smooth dose-response, approximately doubling in each instance as the dose was doubled from 250 to 500 and from 500 to 1,000 mg. High concentrations of cyclacillin were also demonstrated in urine. Neither ratio of drug to metabolite in the urine nor the percent of excretion was significantly affected by the dose level. Sixty-seven percent of the drug was excreted unchanged, and 17% was excreted as penicilloic acid, with most of the excretion occurring within 6 h of administration. In subjects given 500 mg of cyclacillin (four times daily) for 6 days, 2% of the drug was excreted as 1-aminocyclohexanecarboxylic acid, and approximately 55% (24 to 91%) was unchanged. Neither formation nor excretion of the former was sex dependent.