Mecillinam is an amidino penicillinate derivative with a broad spectrum of activity against many gram-negative bacilli. Moreover, marked in vitro synergy against these organisms occurs when mecillinam is combined with other ,B-lactam antibiotics. The purpose of this study was to determine the pharmacokinetic disposition of this antibiotic. A single dose of 10 mg/kg was administered to 12 healthy volunteers as a 15-min intravenous infusion. Multiple plasma and urine samples were collected at frequent intervals for 8 and 24 h, respectively. Plasma samples were assayed for mecillinam by using a specific high-pressure liquid chromatographic assay developed in our laboratory. Peak plasma levels ranged from 34 to 80 Ag/ml, and after 4 h, plasma levels were 0.7 to 1.9 ,g/ml. The mean terminal plasma half-life was 51.1 ± 8.6 min. The mean steady-state volume of distribution was calculated to be 0.23 ± 0.04 liter/kg. The mean plasma and renal clearances were 3.5 ± 0.4 and 2.5 ± 0.4 ml/min per kg, respectively. The mean percentage of the dose excreted unchanged in the urine at 4 h was 67 ± 5%; 71 ± 6% was recovered in 24 h. Urine concentrations at 4 h were far above the minimum inhibitory concentration for susceptible gram-negative organisms.Mecillinam is a new semisynthetic /8-lactam antibiotic. It is a 6-amidinopenicillanic acid, whereas other 8l-lactam antibiotics are 6-acylaminopenicillanic acids. This altered structure has resulted in differences in microbiological activity. Mecillinam is generally more active against gram-negative than gram-positive organisms. The minimum inhibitory concentration of mecillinam for most susceptible strains of gram-negative bacteria is c1 to 2 pg/ml (9). Additionally, this antibiotic exhibits synergistic effects in vitro when combined with other 8-lactam antibiotics such as ampicillin, carbenicillin, or cephalothin (2).The objectives of this study were to determine the pharmacokinetic parameters and excretion characteristics of mecillinam after intravenous administration in healthy subjects. This was accomplished by using a newly developed highpressure liquid chromatographic assay developed by our group for determination of mecillinam in plasma and urine.(This paper was presented in part at the 81st Annual Meeting of the American Society for Clinical Pharnacology and Therapeutics, San Francisco, Calif., March 19, 1980.) MATERIALS AND METHODS Experimental procedure. Twelve healthy adult volunteers participated in this study. Informed consent was obtained from each subject, and guidelines for human experimentation of the U.S. Department of Health, Education, and Welfare and those of our institution were followed in the conduct of this clinical research. A panel of laboratory tests, consisting of an SMA 12, complete blood cell count, differential blood cell count, urinalysis, and creatinine clearance, as well as a complete medical history and physical examination were performed before and after drug administration. Table 1 shows individual subject characteristics. Mecillinam (1-g vial...