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13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.
- Source :
-
International journal of toxicology [Int J Toxicol] 2024 Sep-Oct; Vol. 43 (5), pp. 472-490. Date of Electronic Publication: 2024 Jun 19. - Publication Year :
- 2024
-
Abstract
- The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUC <subscript>last</subscript> and C <subscript>max</subscript> at Day 91) was greater in males than females, suggesting sex differences. AUC <subscript>last</subscript> and C <subscript>max</subscript> at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed T <subscript>max</subscript> and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.<br />Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Subjects :
- Animals
Dogs
Male
Female
Administration, Oral
Toxicokinetics
No-Observed-Adverse-Effect Level
Area Under Curve
Dose-Response Relationship, Drug
Drug Combinations
Toxicity Tests, Subchronic
Rabeprazole pharmacokinetics
Rabeprazole toxicity
Rabeprazole administration & dosage
Sodium Bicarbonate pharmacokinetics
Sodium Bicarbonate toxicity
Sodium Bicarbonate administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1092-874X
- Volume :
- 43
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 38897632
- Full Text :
- https://doi.org/10.1177/10915818241261631