What is the half-life of Qulipta (atogepant)?

Half-Life of Qulipta (Atogepant)

The half-life of Qulipta (atogepant) is approximately 11 hours. 1

Pharmacokinetic Profile of Atogepant

Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the preventive treatment of migraine. Its pharmacokinetic properties include:

• Absorption: Rapidly absorbed with peak plasma concentrations at approximately 1-2 hours after oral administration 1
• Distribution: Mean apparent volume of distribution is approximately 292 L 1
• Metabolism: Primarily metabolized by CYP3A4 1
• Elimination:
  • Half-life of approximately 11 hours 1, 2
  • Mean apparent oral clearance of approximately 19 L/hr 1
  • Following oral dosing, 42% is recovered as unchanged drug in feces and 5% in urine 1

Clinical Implications of Atogepant's Half-Life

The 11-hour half-life of atogepant allows for convenient once-daily dosing, which can improve medication adherence compared to medications requiring multiple daily doses. This pharmacokinetic property supports its FDA-approved dosing schedule for migraine prevention.

Dosing Considerations

• The drug can be taken without regard to food, as high-fat meals only reduce AUC and Cmax by approximately 18% and 22% respectively, with no effect on time to maximum concentration 1
• No significant accumulation occurs with once-daily dosing 1, 2
• For patients with renal impairment, no dose adjustment is needed for mild to moderate impairment (CLcr 30-89 mL/min) 1

Comparison to Other Migraine Medications

Atogepant's 11-hour half-life positions it in the middle range compared to other migraine medications:

• Triptans have variable half-lives, with naratriptan having the longest half-life among triptans 3
• Other CGRP antagonists (gepants) have similar pharmacokinetic profiles, though specific half-lives vary

Safety Considerations Related to Half-Life

The moderate half-life of atogepant contributes to its favorable safety profile:

• Clinical trials have shown that atogepant is generally well-tolerated even at supratherapeutic doses (170 mg) administered daily for 28 days 2
• The most common treatment-emergent adverse events include constipation (6.9-7.7%), nausea (4.4-6.1%), and upper respiratory tract infections (10.3%) 4, 5
• Unlike some earlier CGRP antagonists, atogepant has not been associated with clinically meaningful elevations in liver enzymes 2

Practical Implications for Patients

The 11-hour half-life of atogepant provides several advantages for patients:

• Allows for once-daily dosing, which may improve adherence
• Provides sustained efficacy throughout a 24-hour period
• Minimizes the risk of medication accumulation with regular dosing
• Supports its use as a preventive treatment rather than an abortive therapy

In long-term studies, once-daily atogepant has demonstrated sustained efficacy over 52 weeks, with increasing benefits over time 4, suggesting that the pharmacokinetic profile supports durable clinical response.