Elevations in plasma glucagon are associated with reduced insulin clearance after ingestion of a mixed-macronutrient meal in people with and without type 2 diabetes.

Aims/hypothesis: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear.

Methods: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19).

SAAM II: A general mathematical modeling rapid prototyping environment.

Simulation Analysis and Modeling II (SAAM II) is a graphical modeling software used in life sciences for compartmental model analysis, particularly, but not exclusively, appreciated in pharmacokinetics (PK) and pharmacodynamics (PD), metabolism, and tracer modeling. Its intuitive "circles and arrows" visuals allow users to easily build, solve, and fit compartmental models without the need for coding. It is suitable for rapid prototyping of models for complex kinetic analysis or PK/PD problems, and in educating students and non-modelers.

Physiologically based Pharmacokinetic Model Validated to Enable Predictions Of Multiple Drugs in a Long-acting Drug-combination Nano-Particles (DcNP): Confirmation with 3 HIV Drugs, Lopinavir, Ritonavir, and Tenofovir in DcNP Products.

Drug-Combination Nanoparticles (DcNP) are a novel drug delivery system designed for synchronized delivery of multiple drugs in a single, long-acting, and targeted dose. Unlike depot formulations, slowly releasing drug at the injection site into the blood, DcNP allows multiple-drug-in-combination to collectively distribute from the injection site into the lymphatic system. Two distinct classes of long-acting injectables products are proposed based on pharmacokinetic mechanisms.

Viral dissemination and immune activation modulate antiretroviral drug levels in lymph nodes of SIV-infected rhesus macaques.

Introduction And Methods: To understand the relationship between immunovirological factors and antiretroviral (ARV) drug levels in lymph nodes (LN) in HIV therapy, we analyzed drug levels in twenty-one SIV-infected rhesus macaques subcutaneously treated with daily tenofovir (TFV) and emtricitabine (FTC) for three months.

Results: The intracellular active drug-metabolite (IADM) levels (TFV-dp and FTC-tp) in lymph node mononuclear cells (LNMC) were significantly lower than in peripheral blood mononuclear cells (PBMC) (P≤0.005).

A novel formulation enabled transformation of 3-HIV drugs tenofovir-lamivudine-dolutegravir from short-acting to long-acting all-in-one injectable.

Objective: To develop an injectable dosage form of the daily oral HIV drugs, tenofovir (T), lamivudine (L), and dolutegravir (D), creating a single, complete, all-in-one TLD 3-drug-combination that demonstrates long-acting pharmacokinetics.

Design: Using drug-combination-nanoparticle (DcNP) technology to stabilize multiple HIV drugs, the 3-HIV drugs TLD, with disparate physical-chemical properties, are stabilized and assembled with lipid-excipients to form TLD-in-DcNP . TLD-in-DcNP is verified to be stable and suitable for subcutaneous administration.