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Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics.
Abstract: Gallium (Ga) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate (GaM) would provide a higher bioavailability than oral Ga salts. However, oral administration to adult horses of 2 mg/kg of GaM, in the form of a solution mixed with food, did not lead to detectable Ga levels in plasma. Therefore, a study was performed to model the chemical behaviour of GaM in the digestive tract. The equilibrium formation constants for Ga(III) and maltol were calculated by means of UV–visible measurements and validated by 1H-NMR measurements at selected pH values. Data indicate that the dissociation of GaM in aqueous solutions is very rapid, while the re-association is slower. Based on these results, poor Ga absorption seems to be due to the equilibrium dissociation of GaM in the stomach and to its slow formation rate in the intestine. The concomitant presence of high concentrations of phytates (strong charged metal chelating agents, which represent about 1% of dry matter in vegetables) might also explain the low absorption of GaM by the gastrointestinal tract. Methods of optimizing Ga absorption after oral administration of GaM require further investigation.
Publication Date: 2013-08-29 PubMed ID: 23980593DOI: 10.1111/jvp.12022Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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This research investigates the absorption of gallium maltolate (GaM) when orally administered with food to adult horses, revealing that this method does not result in detectable levels of gallium in plasma, suggesting the need for further investigation in optimizing GaM absorption.
Gallium maltolate and its uses
- Gallium maltolate (GaM) is being studied for its potential use in treating osteolytic disorders in horses.
- Osteolytic disorders refer to conditions characterized by the destruction or dissolving of bone tissue.
- GaM was believed to have higher bioavailability when administered orally compared to other gallium salts. Bioavailability refers to the extent and rate at which the active drug ingredient is absorbed and becomes available at the site of drug action.
Study specifics and findings
- The researchers administered 2 mg/kg of GaM with food to adult horses, but no notable gallium levels were found in blood plasma.
- A subsequent study was conducted to observe and model the chemical behaviour of GaM in the equine digestive system. The formation constants for Ga(III) and maltol (components of GaM) were calculated using UV-visible and 1H-NMR measurements at selected pH levels.
- The data revealed that GaM dissociates quickly in water solutions, but re-associates slowly. This finding suggests that poor Ga absorption is due to GaM dividing in the stomach and its slow formation rate in the intestines.
Additional research implications
- The gastric environment with high concentrations of phytates (approximately 1% of dry substrate in vegetables), which are potent chelating agents, might also contribute to the lower GaM absorption in the gastrointestinal tract.
- Chelating agents are substances that can form several bonds to a single metal ion, making it more difficult for the metal ion to interact with other substances. In this context, the chelating action of phytates might interfere with the absorption of gallium, making GaM less bioavailable.
- These findings suggest a need for additional research to optimize the Ga absorption in the equines after oral administration of GaM.
Cite This Article
APA
Pollina GF, Pepe M, Dean A, Di Marco V, Marton D.
(2013).
Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics.
J Vet Pharmacol Ther, 36(5), 456-461.
https://doi.org/10.1111/jvp.12022 Publication
Researcher Affiliations
MeSH Terms
- Administration, Oral
- Animal Feed
- Animals
- Female
- Horses
- Intestinal Absorption
- Male
- Organometallic Compounds / administration & dosage
- Organometallic Compounds / blood
- Organometallic Compounds / chemistry
- Organometallic Compounds / pharmacokinetics
- Pyrones / administration & dosage
- Pyrones / blood
- Pyrones / chemistry
- Pyrones / pharmacokinetics
Citations
This article has been cited 4 times.- Chen CH, Huang YM, Grillet L, Hsieh YC, Yang YW, Lo KY. Gallium maltolate shows synergism with cisplatin and activates nucleolar stress and ferroptosis in human breast carcinoma cells. Cell Oncol (Dordr) 2023 Aug;46(4):1127-1142.
- Kontoghiorghes GJ. Deferiprone and Iron-Maltol: Forty Years since Their Discovery and Insights into Their Drug Design, Development, Clinical Use and Future Prospects. Int J Mol Sci 2023 Mar 4;24(5).
- Kontoghiorghes GJ, Kolnagou A, Demetriou T, Neocleous M, Kontoghiorghe CN. New Era in the Treatment of Iron Deficiency Anaemia Using Trimaltol Iron and Other Lipophilic Iron Chelator Complexes: Historical Perspectives of Discovery and Future Applications. Int J Mol Sci 2021 May 24;22(11).
- Merli D, Profumo A, Bloise N, Risi G, Momentè S, Cucca L, Visai L. Indium/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone. ACS Omega 2018 Apr 30;3(4):4631-4640.
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