Vildagliptin

MECHANISM OF ACTION

Vildagliptin functions by blocking the DPP-4 enzyme, which breaks down incretin hormones like GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide), both of which are important for regulating blood glucose. 

• Increased Incretin Levels: Inhibiting DPP-4 leads to higher levels of active incretin hormones in the bloodstream.
• Enhanced Insulin Secretion: When blood glucose levels rise, these incretins stimulate insulin release from the pancreas in a glucose-dependent manner.
• Reduced Glucagon Secretion: Vildagliptin lowers glucagon release, which normally increases blood glucose, particularly during fasting.

As a result, vildagliptin helps control blood sugar by stimulating insulin release when needed and reducing glucose production by the liver.

PHARMACOKINETICS

Absorption:

Vildagliptin is quickly absorbed after oral intake, with 85% bioavailability on an empty stomach. Food does not notably impact its absorption.

Distribution:

It has a large volume of distribution (around 71 L) and it is not significantly protein-bound (about 9.3%).

Metabolism:

Vildagliptin undergoes minimal metabolism in the liver. It is primarily converted to an inactive metabolite through hydrolysis and it doesn't rely heavily on cytochrome P450 enzymes for metabolism.

Excretion:

Most of vildagliptin is eliminated unchanged through the urine (about 70% of the dose). A small portion is excreted via feces. The half-life is approximately 2.3 hours and the drug is cleared via both renal and non-renal pathways. In patients with renal impairment, elimination is slower.

DOSAGE AND ADMINISTRATION

The typical starting dose for vildagliptin is 50 mg once daily. The usual maintenance dose is 50 mg once daily. However, the dose can be adjusted depending on individual response and tolerability. The maximum recommended dose is 100 mg per day, taken as 50 mg twice daily or 100 mg once daily.

Renal Impairment:

• Mild: No adjustment needed
• Moderate: 50 mg once daily.
• Severe: Contraindicated.

Administration

• Vildagliptin can be taken with or without food.
• It is typically taken once or twice daily based on the prescribed dose.
• The tablet should be swallowed whole with a glass of water.

DRUG INTERACTIONS

• Other Anti-diabetics: Increased risk of hypoglycemia when combined with sulfonylureas or insulin.
• Rifampin: May reduce effectiveness of vildagliptin.
• Renal-Impacting Drugs: May alter vildagliptin elimination.
• Anti-hypertensive: Additive blood pressure-lowering effects.
• Cytochrome P450 Inhibitors: Minimal interaction due to low involvement with P450 enzymes.

CONTRAINDICATIONS

• Hypersensitivity to vildagliptin or any of its components.
• Severe renal impairment or end-stage renal disease (ESRD).
• Hepatic impairment: Not recommended for patients with moderate to severe liver dysfunction.
• Pregnancy and breastfeeding: Should be avoided

SIDE EFFECTS

Common Side Effects of Vildagliptin:

• Headache
• Dizziness
• Cold
• Upper respiratory tract infections
• Nausea

Serious Side Effects:

• Pancreatitis 
• Severe allergic reactions (e.g., angioedema, anaphylaxis).
• Hepatic dysfunction 
• Hypoglycemia (when combined with other anti-diabetic medications like insulin or sulfonylureas).

TOXICITY

Symptoms of toxicity may include:

• Severe hypoglycemia (especially with insulin or sulfonylureas).
• Liver dysfunction (elevated liver enzymes).
• Kidney issues (especially in those with renal impairment).
• Pancreatitis (severe abdominal pain, nausea and vomiting).
• Management involves supportive care, monitoring blood sugar, liver, and kidney function and discontinuation of the drug if necessary.