In:
The Journal of Clinical Pharmacology, Wiley, Vol. 34, No. 11 ( 1994-11), p. 1053-1059
Abstract:
The safety and pharmacokinetics of E1077, a new injectable cephem antibiotic, were evaluated in healthy male adult volunteers. In the single‐dose studies, 100, 250, 500, 1,000, and 2,000 mg of E1077 were administered by intravenous infusion at a constant rate for 60 minutes, then 1,000 mg of the drug by intravenous infusion at a constant rate for 5 minutes. The C max were 6.4, 15.7 ± 12.0, 34.7 ± 4.6, 63.2 ± 4.6, 142.7 ± 5.6, and 131.6 ± 36.0 (means ± SD) μg/mL, respectively, and the C max and AUC increased linearly with the dose. Plasma concentration‐time curves were well described by a two‐compartment open model. The plasma elimination half life of the drug was 1.88 ± 0.15 hours. The mean urinary recovery within the first 24 hours was 94.1 ± 5.1% of the dose. In the multiple‐dose study, 2,000 mg of E1077 was intravenously administered at a constant rate over 60 minutes every 12 hours for 4.5 days (a total of nine times). The C max after the first and ninth doses were 134.0 ± 17.4 and 135.5 ± 15.5 μg/mL, respectively, and trough levels in day 1 and day 5 (at 12 hours after the first and ninth administration, respectively) were 2.2 ± 0.8 and 1.9 ± 0.4 μg/mL, respectively. No accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between the single‐ and multiple‐dose regimens. The ratio of the concentrations of the diastereomers of A and B forms measured in the plasma or urine at each point of measurement was equal to that of the standard sample, and no difference was observed in the pharmacokinetics of E1077 between the two diastereomers. The fraction of the drug bound to plasma protein was independent of the total plasma concentration and was calculated as 14.5 ± 2.9%. There were no subjective or objective abnormal findings definitely related to the drug, except that two subjects reported mild feelings of sickness during the infusion.
Type of Medium:
Online Resource
ISSN:
0091-2700
,
1552-4604
DOI:
10.1002/jcph.1994.34.issue-11
DOI:
10.1002/j.1552-4604.1994.tb01980.x
Language:
English
Publisher:
Wiley
Publication Date:
1994
detail.hit.zdb_id:
2010253-7
SSG:
15,3
