Does Gastric Lipase Protein (GLP) impact lurasidone absorption?

Impact of GLP-1 on Lurasidone Absorption

GLP-1 receptor agonists can significantly impact lurasidone absorption by delaying gastric emptying, potentially reducing the bioavailability of lurasidone which requires food for optimal absorption.

Mechanism of Interaction

GLP-1 receptor agonists affect drug absorption through several key mechanisms:

• Delayed gastric emptying: GLP-1 receptor agonists activate receptors on the myenteric plexus, inhibiting vagal activity on the gut 1
• Reduced gastric motility: This leads to reduced phasic gastric contractions and increased pyloric tone 1
• Altered gastric environment: GLP-1 RAs cause reduced gastric acid secretion and increased gastric volumes 1

These effects are particularly relevant to lurasidone because:

• Lurasidone requires administration with at least 350 calories of food to optimize bioavailability 2
• When taken without food, lurasidone's bioavailability is significantly reduced - geometric mean Cmax in fasted state was only 56.7 ng/mL compared with 123.0 ng/mL with an 800-1000 kcal meal 2

Differential Impact Based on GLP-1 RA Type

The impact on lurasidone absorption varies by GLP-1 RA formulation:

• Short-acting GLP-1 RAs (exenatide twice daily, lixisenatide):

  • Have more pronounced effects on gastric emptying 3
  • May have greater impact on lurasidone absorption

• Long-acting GLP-1 RAs (liraglutide, semaglutide, dulaglutide):

  • Experience tachyphylaxis (diminishing effect) on gastric emptying over time 1, 3
  • May have less impact on lurasidone absorption with continued use

Clinical Management Strategies

To optimize lurasidone effectiveness when used with GLP-1 RAs:

1. Timing separation: Administer lurasidone at least 1-2 hours before GLP-1 RA administration 3

2. Ensure adequate caloric intake: Lurasidone should be taken with at least 350 calories to ensure maximum exposure 2

   • Studies show similar lurasidone exposure with meals containing 350-1000 calories, regardless of fat content 2

3. Monitor for reduced efficacy: Be alert for signs of reduced lurasidone effectiveness, which may indicate absorption issues

4. Consider dosage adjustments: Higher lurasidone doses may be necessary when co-administered with GLP-1 RAs, especially short-acting ones

Special Considerations

• Patients with bariatric surgery: These patients may already have altered drug absorption and may experience more pronounced effects when adding GLP-1 RAs 4

• Patients with gastroparesis: GLP-1 RAs are not recommended in patients with clinically meaningful gastroparesis 1, and the combination with lurasidone may further complicate absorption

• Tachyphylaxis: The diminishing effect of long-acting GLP-1 RAs on gastric emptying over time may reduce the interaction with lurasidone with continued use 1, 3

Monitoring Recommendations

• Assess for changes in psychiatric symptoms that might indicate reduced lurasidone effectiveness
• Monitor for metabolic parameters, as both medications can affect weight and glucose metabolism 5
• Consider therapeutic drug monitoring if available when initiating or adjusting either medication