Pharmacokinetics of Ranitidine after Partial Gastrectomy in Dogs

Makil, Olivier; Kaltenbach, Matthieu L.; Limberg, Jobst; Harrison, Douglas A.; Hocking, Michael P.; Derendorf, Hartmut

doi:10.1002/jps.2600801107

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…This study included six adult domestic shorthair cats that were part of a previously published study that evaluated the effect of chronic oral omeprazole administration on serum calcium, magnesium, cobalamin, and gastrin concentrations and bone mineral density in cats ( 25 ). Six cats were included in the pilot study as this is the suggested minimum number of patients necessary to perform pharmacological studies ( 26 ). The Institutional Animal Care and Use Committee at the University of Tennessee approved the protocol for this study (32312-0115).…”

Section: Methodsmentioning

confidence: 99%

Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study

et al. 2018

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Although they have historically been thought of as safe medications, proton pump inhibitors such as omeprazole have been associated with an increased risk of enteric, particularly Clostridium difficile, infections in people. In cats, omeprazole is often the first choice acid suppressant prescribed for the treatment of upper gastrointestinal (GI) ulceration and bleeding. Despite this, no studies to date have explored the effect of omeprazole on the feline fecal microbiome and metabolome. Therefore, the purpose of this pilot study was to evaluate the effect of prolonged omeprazole administration on the fecal microbiome and metabolome in healthy cats to identify targets for analysis in a larger subset of cats with GI disease. A within-subjects, before and after, pilot study was performed whereby six healthy adult cats received 60 days of placebo (250 mg lactose PO q 12 h) followed by 5 mg (0.83–1.6 mg/kg PO q 12 h) omeprazole. On days 0, 30, and 60 of placebo and omeprazole therapy, the fecal microbiome and metabolome were characterized utilizing 16S ribosomal RNA sequencing by Illumina and untargeted mass spectrometry-based methods, respectively. Omeprazole administration resulted in no significant changes in the global microbiome structure or richness. However, transient changes were noted in select bacterial groups with omeprazole administration resulting in an increased sequence percentage of Streptococcus, Lactobacillus, Clostridium, and Faecalibacterium spp. and a decreased sequence percentage of Bifidobacterium spp. Significance was lost for all of these bacterial groups after adjustment for multiple comparisons. The fecal concentration of O-acetylserine and aminomalonate decreased with omeprazole therapy, but significance was lost after adjustment for multiple comparisons. The results of this pilot study conclude that omeprazole has a mild and transient impact on the fecal microbiome and metabolome when orally administered to healthy cats for 60 days. Based on the findings of this pilot study, evaluation of the effect of omeprazole specifically on Streptococcus, Lactobacillus, Clostridium, Faecalibacterium, and Bifidobacterium spp. is warranted in cats with primary GI disease.

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Section: Methodsmentioning

confidence: 99%

Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study

et al. 2018

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“…Pharmacokinetic parameters were compared in five dogs (5 mg/kg) (Makil et al, 1991) and six young human (150 mg) (Hockings and Stevenson, 1982) after oral administration of ranitidine. Elimination t 1/2 is 2.5 ± 0.3 h in dogs compared to 2.2 ± 0.4 h in humans, resulting in the mean ratio of 1.1.…”

Section: B Ranitidine -Pharmacokinetic Comparisonmentioning

confidence: 99%

Assessing human health risks of chemicals and drugs: An overview

Suh

Abdel‐Rahman

1997

Human and Ecological Risk Assessment: An International Journal

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The risk assessment process for non-carcinogens involves extrapolation of toxicological animal data to humans by applying uncertainty factors (UF). A 10-fold UF is most commonly used to account for underlying variability in different areas of uncertainty. The purpose of this investigation is to evaluate whether the magnitude of the 10X UF can be reduced when pharmacokinetic and pharmacodynamic data are incorporated especially into interspecies extrapolation and interindividual variability. A compilation and comparison of kinetic and dynamic data between animal/human and sensitive human/human were made. The composite UFs were calculated using the highest ratios for available kinetic and dynamic data and default subfactors. When relevant kinetic and dynamic data are available, UFs are significantly reduced by replacing the default factors with actual data derived-values.

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Pharmacokinetics of Ranitidine after Partial Gastrectomy in Dogs

Cited by 2 publications

References 15 publications

Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study

Omeprazole Minimally Alters the Fecal Microbial Community in Six Cats: A Pilot Study

Assessing human health risks of chemicals and drugs: An overview

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