ArticlePharmaceutical research2008
Species difference in intestinal absorption mechanism of etoposide and digoxin between cynomolgus monkey and rat.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 23 citations in OpenAlex.
- Conversion of Olmesartan to Olmesartan Medoxomil, A Prodrug that Improves Intestinal Absorption, Confers Substrate Recognition by OATP2B1.Pharmaceutical research · 2024Article
- Consideration of Fractional Distribution Parameter fPharmaceutical research · 2022Article
- Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys.Pharmaceutical research · 2018Article
- Effect of coadministration of rifampicin on the pharmacokinetics of linezolid: clinical and animal studies.Journal of pharmaceutical health care and sciences · 2018Article
- Pharmacokinetics and toxicity of repeated oral etoposide is altered by morphine coadministration in rats.European journal of drug metabolism and pharmacokinetics · 2015Article
- pH Dependent but not P-gp Dependent Bidirectional Transport Study of S-propranolol: The Importance of Passive Diffusion.Pharmaceutical research · 2015Article
- Inhibition of OCTN2-mediated transport of carnitine by etoposide.Molecular cancer therapeutics · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe oral bioavailability of some therapeutic agents is markedly lower in cynomolgus monkeys than in humans. We investigated small-intestinal absorption of the P-glycoprotein (P-gp) substrates etoposide and digoxin in monkeys to clarify the influence of efflux transport on their intestinal permeability.
methodsThe pharmacokinetics of etoposide and digoxin was examined in monkeys and rats after oral and intravenous administration. Intestinal permeability and segmental differences in permeability were investigated with an Ussing-type chamber.
resultsThe bioavailability of etoposide was 12.9 and 13.9% in monkeys and rats, respectively. Total body clearance of etoposide in monkeys was much less than hepatic blood flow, suggesting that the bioavailability would be limited at intestinal absorption. Marked vectorial transport of etoposide in the secretory direction was observed in rats, especially in the lower small intestine, and segmental differences were consistent with the distribution of P-gp expression. Vectorial transport was minimal in monkey small intestine. Our kinetic analysis indicated that P-gp contributes little to the intestinal permeability of etoposide and digoxin in monkeys, and apical uptake is rate-limiting.
conclusionLow bioavailability of etoposide in monkeys is due to poor intestinal uptake resulting from low influx from the apical side, rather than secretion via P-gp.
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Registered trials
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