Preclinical rodent toxicity studies for long term use of ceftriaxone
| Autor: | James D. Berry, Lorena Loci, Elena Ratti, Jeremy M. Shefner, Amy Swartz Ellrodt, Merit Cudkowicz, David J. Greenblatt |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
Urinalysis Anemia Health Toxicology and Mutagenesis Pharmacology Toxicology Gastroenterology Article 03 medical and health sciences Subcutaneous injection 0302 clinical medicine Pharmacokinetics lcsh:RA1190-1270 Internal medicine medicine Amyotrophic lateral sclerosis (ALS) lcsh:Toxicology. Poisons 030304 developmental biology 0303 health sciences Hematology Rodent medicine.diagnostic_test business.industry Stomach Ceftriaxone medicine.disease 3. Good health Preclinical study medicine.anatomical_structure Toxicity business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicology Reports Toxicology Reports, Vol 2, Iss C, Pp 1396-1403 (2015) |
| ISSN: | 2214-7500 |
| DOI: | 10.1016/j.toxrep.2015.09.010 |
| Popis: | A 6-month rodent toxicology and pharmacokinetic (PK) study was performed to provide supportive safety data for long-term use of intravenous ceftriaxone in a clinical trial in patients with amyotrophic lateral sclerosis (ALS). Ceftriaxone was administered by subcutaneous injection at up to 2 g/kg/day to Sprague-Dawley Crl:CD (SD) rats. Ceftriaxone was found to be safe and well tolerated. Specifically, no significant differences in body weight and food consumption were observed between the treatment and control groups. With the exception of in red cell parameters decrease, there were no ceftriaxone-related changes in hematology, coagulation, clinical chemistry and urinalysis parameters. Injection site trauma and associated reversible anemia, likely due to chronic blood loss at the injection site, were all attributable to subcutaneous route of administration. Cecum dilatation and some skin changes were reversible after recovery period, while bile duct dilatation, observed only in a few animals, persisted. Changes in the non-glandular stomach do not have a human correlate. The no-observed-adverse-effect dose level (NOAEL) was 0.5 g/kg/day ceftriaxone in both sexes. Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 hours. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 hours after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months) of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials. |
| Databáze: | OpenAIRE |
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