Pharmacokinetic studies with mecillinam and pivmecillinam.

Mecillinam (FL 1060) is a new beta-lactam antibiotic particularly active against gram-negative organisms. When given intravenously, very high serum levels were maintained for a short period of time. Lower peak levels but comparable bioavailability were obtained after intramuscular administration. Gastrointestinal absorption of mecillinam is poor, and for effective oral therapy the drug must be given in the form of its pivaloyl-oxymethyl ester pivmecillinam (FL 1039) which is well absorbed and rapidly transformed to mecillinam by enzymatic hydrolysis in the body. Urinary recovery of mecillinam after orally administered pivmecillinam was 45% in the first 6 h compared with 55 and 59% after mecillinam given by the intravenous and intramuscular routes, respectively. By increasing the dose the orally active ester produced proportionally higher levels of mecillinam, and the area under the serum curve was doubled with the dose. Higher peak levels and prolonged maintenance of high serum concentrations were seen after administration of pivmecillinam with probenecid. The presence of food in the stomach did not influence the absorption of pivmecillinam to any great extent.

Clinical pharmacology of pivampicillin.

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 mug/ml at 56 min with pivampicillin and 1.96 mug/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 mug/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.