Use of a long-term continuous glucose monitor for predicting sulfonylurea dose in patients with neonatal diabetes mellitus: a case series.

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes that presents with uncontrolled hyperglycemia during the first 6 months of life. NDM is a rare disease in which gene variants mainly cause ß-cell loss or dysfunction (6q24 duplication, KCNJ11, and ABCC8). Although NDM is primarily treated through insulin therapy, it is highly challenging to manage blood glucose levels using insulin therapy during infancy. In contrast, KCNJ11 and ABCC8 mutant patients received oral sulfonylureas (SU) instead of insulin injections; however, the dose and frequency differ among individuals. Continuous glucose monitoring (CGM) is useful in patients with type 1 diabetes; but reports on patients with NDM are lacking. Herein, we report two cases of NDM with the KCNJ11 variant. We used CGM not only during insulin injection therapy but also after switching to oral SU therapy. The CGM data can also be used to determine the dose and frequency of SU. Furthermore, long-term CGM may be useful for adjusting SU dose and frequency, and maintaining good glycemic control not only during insulin injection but also during oral SU therapy.

Prediction of oral absorption of low-solubility drugs by using rat simulated gastrointestinal fluids: the importance of regional differences in membrane permeability and solubility.

PURPOSE: This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs by considering regional differences in solubility and permeability within the gastrointestinal (GI) tract. METHODS: Simulated GI fluids were prepared to reflect rat in vivo bile acid and phospholipid concentrations in the upper and lower small intestine. The saturated solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug with low aqueous solubility, were measured using these simulated fluids, and fraction absorbed (Fa) at time t after oral administration was calculated. RESULTS: The saturated solubility of GF and AZ, a drug with low aqueous solubility, differed considerably between the simulated GI fluids. Large regional differences in drugs concentration were also observed following oral administration in vivo. The predicted Fa values using solubility and permeability data of the simulated GI fluid were found to correspond closely to the in vivo data. CONCLUSION: These results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately. The new methodology developed in the present study could be useful for new oral drug development.