PHASE I STUDY OF CEFDINIR

• Published in: CHEMOTHERAPY Vol. 37; no. Supplement2; pp. 208 - 245
• Main Authors: SHISHIDO, AKIRA, TSUNOO, MICHIO, SHIMADA, KAORU
• Format: Journal Article
• Language: English; Japanese
• Published: Japanese Society of Chemotherapy 1989; 公益社団法人 日本化学療法学会
• Subjects: Cefdinir; 体内動態; 単回投与; 忍容性; 連続投与
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.37.Supplement2_208

The safety and pharmacokinetics of cefdinir (CFDN), a new oral cephalosporin derivative, were examined in healthy male volunteers in a single- or multiple- dose study. In the single- dose study, 9 subjects were given an oral dose of 50, 100 or 200mg of CFDN in a fasting state. In the multiple- dose study, 9 subjects were divided into two groups of 6 for CFDN treatment, and 3 for placebo treatment. The subjects from the active or placebo group were given 200mg of CFDN or placebo t.i.d. after meals for 14 days and once on day 15. 1. CFDN was well tolerated by all subjects. Only minor adverse effects, such as soft stool or muddy stool, and slight elevations of WBC and transaminase were observed respectively in two, one, and two subjects from the active group during multiple dosing. These events were not considered clinically significant. 2. Great changes in fecal bacterial flora, especially anaerobes, due to the antibacterial activity of CFDN were observed during multiple dosing. The bacterial flora returned to normal seven days after the last dose. 3. The plasma concentration of CFDN peaked at 3.9 h after single dosing and decreased monoexponentially with a half-life of 1.71 h. After a dose of 50, 100, or 200mg, the AUC was 3.40, 5.78, or 9. 23μg·h/ml, and urinary recovery was 33.3%, 30.8%, or 25.9% of the dose, respectively. A slight decrease in absorption of CFDN was observed after a dose of 200mg. 4. With multiple dosing, Cmax, Tmax, AUC, and renal clearance did not differ significantly between the first and last doses. The trough concentration and urinary excretion reached a steady state by day 2. 5. Active metabolites of CFDN were not detected in the plasma, urine or feces.