Phase I study of E1040, a new parenteral cephem antibiotic.
The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated.
Nakashima
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Uematsu
T
T
Kanamara
M
M
Ueno
K
K
Setoyama
T
T
Tomono
Y
Y
Ohno
T
T
Okano
K
K
Morishita
N
N
D000328:Adult; D001681:Biological Assay; D002511:Cephalosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004341:Drug Evaluation; D005243:Feces / Q000032:analysis; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male
D002511:Cephalosporins; C056494:cefclidin