Mirtazapine Half-Life
The elimination half-life of mirtazapine in adults ranges from 20 to 40 hours, allowing for once-daily dosing at bedtime. 1
Pharmacokinetic Profile
Mirtazapine exhibits an elimination half-life of approximately 20-40 hours following oral administration, with steady-state plasma concentrations achieved within 4-5 days due to approximately 50% drug accumulation (accumulation ratio = 1.5). 1, 2
Peak plasma concentrations are reached within approximately 2 hours after oral administration, with an absolute bioavailability of about 50% due to first-pass metabolism. 1, 2
The drug demonstrates linear pharmacokinetics over the therapeutic dose range of 15-80 mg, making dosing adjustments predictable. 1, 2
Enantioselective Pharmacokinetics
The pharmacokinetics of mirtazapine are enantioselective, with the (R)-(-)-enantiomer having an elimination half-life approximately twice as long (18.0 ± 2.5 hours) compared to the (S)-(+)-enantiomer (9.9 ± 3.1 hours). 2
The (R)-(-)-enantiomer achieves plasma levels approximately 3 times higher than the (S)-(+)-enantiomer due to its longer half-life. 1
Gender and Age Differences
Females exhibit significantly longer elimination half-lives than males (mean half-life of 37 hours for females versus 26 hours for males across all age groups). 1
Elderly patients demonstrate reduced oral clearance compared to younger adults: clearance is 40% lower in elderly males and 10% lower in elderly females compared to their younger counterparts. 1
Special Populations Affecting Half-Life
Renal impairment significantly affects clearance: total body clearance is reduced approximately 30% in patients with GFR 11-39 mL/min/1.73 m² and approximately 50% in patients with GFR <10 mL/min/1.73 m², which would prolong the half-life proportionally. 1
Hepatic impairment decreases oral clearance by approximately 30%, resulting in a prolonged elimination half-life. 1
Clinical Implications
The 20-40 hour half-life enables once-daily bedtime dosing, which is the recommended administration schedule. 1, 3
Steady-state is reached within 4 days in adults and 6 days in the elderly, reflecting the drug's accumulation characteristics. 4
The prolonged half-life means that dose adjustments should not be made more frequently than every 4-5 days to allow adequate time to reach new steady-state concentrations. 1