Blood levels of cefazolin and cephalothin were determined in two separate crossover studies in 20 healthy male adults, each after intravenous and intramuscular administration. Pharmacokinetic parameters were calculated from the intravenous data based upon a two-compartment open model. The rate constants controlling the distribution between the central and peripheral compartments, the overall elimination rate constants, the apparent volumes of distribution, and the fraction of the dose in the central and peripheral compartments were determined. The bioavailability was calculated to be 100% for cefazolin and cephalothin.Cefazolin is a new broad-spectrum cephalosporin antibiotic derived from 7-amino cephalosporanic acid, which has a wide range of activity against gram-positive and gram-negative pathogens. It was synthesized and studied extensively in Japan (6, 11-13, 16) before being developed for clinical use in the United States. Pharmacokinetic studies in normal subjects have shown higher and more prolonged serum levels with cefazolin than with other cephalosporin antibiotics, e.g., cephaloridine and

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Pharmacokinetic parameters were calculated from intravenous data based upon a two-compartment open model. These parameters were subsequently used to determine the absorption rates and bioavailability of cephradine administered intramuscularly and orally. The results indicate that cephradine obeys dose-independent kinetics and that biological availability is complete from all dosage forms.Cephradine, a semisynthetic cephalosporin derivative chemically designated as 7-[D-2-amino(1,4 -cyclohexadien -1 -yl)acetamido] -3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, is structurally similar to cephalexin (Fig. 1). The compound is well absorbed from the gastrointestinal tract irrespective of the presence of food (3) and is effective in the treatment of both animal (1, 6) and human bacterial infections (4, 5). Cephradine is acid stable (1) and, after oral administration in mice, is rapidly absorbed and excreted virtually unchanged in the urine (10). Binding of cephradine to human plasma proteins is reversible and is less than 20% in vitro (7). The purpose of this paper is to elucidate the pharmacokinetics in humans and to determine the bioavailability of the drug administered intramuscularly and orally at various dosage levels in capsule and suspension forms. MATERIALS AND METHODSIntravenous administration. Each of eight fasting, normal, adult male subjects, ranging in age from 22 to 39 years and weighing between 145 and 188 pounds (ca. 65.8 and 85.3 kg), was given a single 1,000-mg dose of cephradine intravenously. Blood samples were taken prior to drug administration and at 5, 15, 30, 60, 120, 240, and 360 min after administration.Urine samples were collected prior to drug administration and for the time periods 0 to 2, 2 to 4, and 4 to 6 h after injection of the drug.Blood and urine samples were collected, frozen, and then analyzed for drug concentration by a Bacillus subtilis agar disk plate method (2).Intramuscular administration. Each of 20 fasting, normal, adult male subjects, ranging in age from 20 to 60 years and weighing between 145 and 195 pounds (ca 65.8 and 86.5 kg), received a single 1,000-mg dose of cephradine intramuscularly. Blood samples were obtained prior to drug administration and at 15, 30, 45, 60, 90, 120, 150, 180, 240, and 360 min after injection.Urine samples were collected prior to drug administration and for the time periods 0 to 2, 2 to 4, and 4 to 6 h after injection of the drug.Blood and urine samples were collected, frozen, and then analyzed as described in the intravenous study.Oral administration. A crossover study was carried out in 20 normal, adult male subjects ranging in age from 21 to 54 years and weighing between 140 and 208 pounds (ca. 63.5 and 94.3 kg). On test day 1, each subject was given either a single 250-mg or a 500-mg capsule according to a randomized dosing schedule. The subjects fasted 8 h before and 3 h after administration of the drug. Blood samples were taken prior to drug ingestion and at 30, 60, 90, 120, 180, and 360 min after administration. ...