Pharmacokinetic Interpretation of Cephradine Levels in Serum After Intravenous and Extravascular Administration in Humans

Abstract

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. ...

Bioavailability, pharmacokinetics and tissue residues of cephradine (Atocef Forte®) in healthy and colisepticemic broiler chickens

“…in healthy chickens showed that, the disposition best fitted by a two compartments open model. The obtained result was consistent with that reported for cephradine in human (Rattie et al, 1976) and goats (El-Sayed et al 1994). In this study, the Vdss for cephradine was 321.53 mL/kg, suggesting a higher penetration through biological membranes and tissue after IV injection in broiler chickens.…”

“…Cephradine half-life is reported to range from 0.6 to 1.8 hours (Wise, 1990). The pharmacokinetics of cephradine were investigated in mice, rats, dogs (Weliky et al, 1974), human (Rattie et al, 1976;Roberts et al, 1981), foals (Henry et al, 1992), goats (El-Sayed et al, 1994) and chickens (El-Sayed et al, 2016). To our knowledge, only a few studies about disposition of cephardine in broilers are available.…”

Pharmacokinetics of Oral Cephalosporins: Cephradine and Cephalexin

“…Rattie et a l . (10) demonstrated that a linear relationship between dose (0.25-1.0 g) and both peak concentration and AUC exists for cephradine. Pfeffer et al (9) reported that a linear relationship in peak concentration and AUC exists for cephalexin a t doses of 0.25 and 0.5 g. The reported pharmacokinetic parameters from these studies are similar to the present findings; therefore, dose-dependent kinetics do not appear to exist with these drugs.…”

An Open‐Label, Randomized, 2‐Way, Crossover Bioequivalence Study of Cefradine Capsules in Healthy Chinese Volunteers

“…Food in the gastrointestinal tract may delay the absorption of cefradine, but the total amount of absorption will not be affected. PK parameters of oral cefradine capsules reported in prior research [13][14][15][16][17][18][19] were remarkably similar, and the concentrations of different doses of cefradine capsules approached the peak about 1 hour after fasting oral administration. The data from the current study showed that peak time was reached about 2.5 hours after administration, and the half-life was about 1 hour.…”

“…Rattie et al 13 showed the results from a doublecrossover study of 20 volunteers treated with oral 250or 500-mg cefradine capsules and 22 volunteers treated with 1000-mg cefradine capsules, the PK characteristics of the 250-and 1000-mg cefradine capsules were linearly correlated. A bioequivalence study 11 of 500mg cefradine capsules orally administered under the fasting conditions for 24 healthy volunteers in Korea also showed the similar results compared with the reference preparation, as the test and reference preparations were found to be bioequivalent.…”