Gastro-resistant mixed micelles allow sufficient and reliable oral vitamin K absorption under cholestatic conditions, according to the results of a study published in Gastroenterology.
To prevent life-threatening vitamin K deficiency bleedings (VKDBs) in infancy, vitamin K prophylaxis is offered worldwide to newborns. The limitations of this treatment are described by the authors: “Intramuscular injection is an efficacious treatment option, but overall effectiveness is hampered by increasing rates of parental refusal. Oral administration is well tolerated, but is associated with prophylactic failures in newborns with unrecognized cholestatic liver diseases (1:2,500 live births).”
In this study, researchers provide in vivo evidence on how and why current prophylactic regimens fail to ensure effective vitamin K absorption under cholestatic conditions. In addition, investigators demonstrate how gastro-resistant mixed micelles could be used to overcome the limitations of current prophylactic vitamin K formulations.
Researchers developed gastro-resistant mixed micelles through PEGylation, by replacing part of the phospholipid content by 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG, a PEGylated phospholipid), or via improved electrostatic repulsion with taurocholic acid, either with or without PEGylation via D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, PEGylated vitamin E). Formulation colloidal stability was carefully inspected in vitro and assessed in vivo for the ability to facilitate vitamin K absorption in cholestatic and sham rat models.
In cholestatic rats, vitamin K absorption from the oil-based formulation was negligible (area under the curve [AUC]0-5hr, 0.004; percent coefficient of variation [%CV], 50 µg-hr/ml). Under these conditions, vitamin K absorption from the mixed micellar product Konakion® MM was noted to be strongly reduced, but also strikingly variable (AUC0-5hr, 0.02; %CV, 23,062 µg-hr/ml).
In sham operated rats, the AUCs of the gastro-resistant formulations and Konakion® MM were comparable. However, under cholestatic conditions, gastro-resistant formulations greatly enhanced vitamin K absorption compared with Konakion® MM.
The study authors concluded that current prophylactic regimens fail to ensure effective vitamin K absorption under cholestatic conditions. In contrast, gastro-resistant mixed micelles enhance vitamin K absorption under cholestatic conditions.
Disclosure: Some study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.
Disclosure. This research was supported by Tiofarma BV. Please see the original reference for a full list of disclosures.
Rooimans T, Minderhoud TC, Leal N, et al. Novel orally formulated mixed micelles optimize vitamin K absorption under bile deficient conditions. Gastroenterol. Published online. doi: 10.1053/j.gastro.2021.05.056