Current Drug Metabolism - Volume 26, Issue 6, 2025

Diabetes mellitus, a widespread and chronic metabolic condition, creates significant challenges for healthcare systems due to complications from inadequate glycemic control, patient non-compliance, and the invasive nature of traditional treatments, including oral medications and insulin injections, which often lead to discomfort, variability in blood glucose levels, and low adherence.

To explore the potential of Transdermal Drug Delivery Systems (TDDS) as a non-invasive and effective alternative for diabetes management, highlighting their advantages, recent technological advancements, and associated challenges.

This review examines the role of TDDS in diabetes treatment, with an emphasis on recent innovations, including microneedles, hydrogels, and sonophoresis. The study also discusses the benefits of TDDS in maintaining stable plasma drug levels, reducing first-pass metabolism, and integrating with continuous glucose monitoring systems.

Emerging TDDS technologies improve drug permeability, enhance bioavailability, and offer sustained drug release, potentially addressing limitations of conventional delivery methods. However, barriers such as skin permeability, high manufacturing costs, and patient variability remain significant challenges.

Multi-drug patches and microneedle-based systems represent innovative approaches that enhance therapeutic efficacy and patient compliance by enabling painless, targeted, and combination drug delivery. With support from nanotechnology and pharmacogenomics, these platforms are evolving toward personalized medicine, offering optimized dosing and reduced side effects.

TDDS presents a promising alternative for diabetes management by improving patient adherence, ensuring controlled drug release, and reducing discomfort associated with injections. While further research is required to overcome existing limitations, advancements in biomaterials and personalized medicine approaches hold the potential to optimize TDDS for widespread clinical application. This research aims to summarize the advancements and address existing challenges for future development.

Shenlian formula (SL) has been widely used to treat various diseases, including type 2 diabetes mellitus and atherosclerosis (AS). Pathological states can significantly alter drug pharmacokinetics (PK) compared to normal physiology, primarily by modulating biological membrane permeability and metabolic enzyme activity, thereby affecting drug absorption, distribution, metabolism, and excretion. However, the specific influence of AS on the PK profile of SL remains uncharacterized.

To investigate the plasma PK of five components (Salvianolic acid A (SAA), Danshensu (DSS), Andrographolide (AND), Neoandrographolide (NAND), and Dehydrated andrographolide (DDAND),) which were the ingredients of SL, in physiological and AS rats administered SL intragastrically.

The AS SD rat model was induced with a high-fat diet, carotid balloon injury, and VD3 injections. A validated LC-MS/MS method quantified plasma concentrations to assess PK parameters.

The validation parameters were all in accordance with the current standards. Comparative PK analysis revealed significant intergroup disparities between the AS and normal groups. The value of Cmax and AUC0-t for DSS was significantly decreased (P<0.05) in the AS group, which indicated that the absorptive amount in vivo was remarkably attenuated in the pathological state. Additionally, the variation trend of AND under Cmax and AUC0-t values were consistent with the alteration trend of DSS. Furthermore, the Tmax of NAND in the AS group was significantly reduced (P<0.05), confirming that the pathological state accelerated the absorption rate of NAND, thereby shortening the time required for NAND to reach its maximum concentration in the body.

We established and validated a sensitive LC-MS/MS method for the simultaneous quantification of five bioactive components of SL in rat plasma. This method is applicable to both physiological and pathological states. Comparative pharmacokinetic analysis revealed significant differences in the systemic exposure of all five analytes between AS and normal rats. These findings provide critical PK evidence for optimizing SL dosage regimens in AS patients, underscoring the imperative to consider the disease’ status when determining therapeutic strategies for traditional Chinese medicine formulations.

Remimazolam is a short-acting sedative/anesthetic. For safe breastfeeding, information on the extent and possible risks of remimazolam being passed over to the infant through mother´s milk is needed. The objective of this work was to study the transfer of remimazolam from maternal to infant circulation by mother´s milk in an animal model.

Three lactating British milk sheep received intravenous remimazolam (0.4 mg/kg bolus plus 4-hr-infusion at 1 or 2 mg/kg/hour). Drug profiles were recorded in plasma and milk. Six suckling lambs were administered remimazolam by intravenous and oral gavage administration for a comparison of plasma concentration profiles of remimazolam and its primary metabolite, CNS7054.

Treatment of lactating sheep induced dose-dependent sedation and loss of consciousness. At the end of infusion, the concentration of remimazolam was higher in milk than in plasma. The subsequent elimination of remimazolam from milk was rapid, although somewhat slower than from plasma.

In lambs, intravenous, but not oral, remimazolam (2 mg) caused different grades of sedation/anesthesia (fully reversible within 8 to 15 min). Mean plasma Cmax was 278.3 ng/mL after intravenous and 1.3 ng/mL after oral administration. Oral gavage resulted in a sizable plasma concentration of CNS7054 (Cmax around 100 ng/mL), indicating efficient intestinal absorption of the parent drug, followed by extensive first-pass metabolic elimination, leading to negligible bioavailability of oral remimazolam.

In mother´s milk, remimazolam reaches higher concentrations than in plasma and is cleared by redistribution to the central compartment for final hepatic elimination. In lambs, oral remimazolam results in minimal plasma concentrations, suggesting that safety concerns regarding breast-fed infants would be minor and could be completely alleviated by a short nursing interruption.