Ranitidine pharmacokinetics and molecular data

Pharmacokinetics
Metabolism Absorption Geriatric Pediatrics Gender Race Renal Insufficiency Hepatic Insufficiency

Metabolism
Mirtazapine is extensively metabolized after oral administration. Major pathways of biotransformation are demethylation and hydroxylation followed by glucuronide conjugation. In vitro data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas cytochrome 3A is considered to be responsible for the formation of the N-desmethyl and N-oxide metabolite. Mirtazapine has an absolute bioavailability of about 50%. It is eliminated predominantly via urine (75%) with 15% in feces. Several unconjugated metabolites possess pharmacological activity but are present in the plasma at very low levels. The (–) enantiomer has an elimination half-life that is approximately twice as long as the (+) enantiomer and therefore achieves plasma levels that are about three times as high as that of the (+) enantiomer. Return to top

Plasma levels
Plasma levels are linearly related to dose over a dose range of 15–80 mg. The mean elimination half-life of mirtazapine after oral administration ranges from approximately 20–40 hours across age and gender subgroups, with females of all ages exhibiting significantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males). Steady state plasma levels of mirtazapine are attained within 5 days, with about 50% accumulation (accumulation ratio = 1.5). Return to top

Absorption
Ranitidine are rapidly and completely absorbed following oral administration and have a half-life of about 20–40 hours. Peak plasma concentrations are reached within about 2 hours following an oral dose. The presence of food in the stomach has a minimal effect on both the rate and extent of absorption and does not require a dosage adjustment. Return to top

Geriatric
Following oral administration of Ranitidine 20 mg/day for 7 days to subjects of varying ages (range, 25–74), oral clearance of mirtazapine was reduced in the elderly compared to the younger subjects. The differences were most striking in males, with a 40% lower clearance in elderly males compared to younger males, while the clearance in elderly females was only 10% lower compared to younger females. Caution is indicated in administering Ranitidine to elderly patients. Return to top

Pediatrics
Safety and effectiveness of mirtazapine in the pediatric population have not been established. Return to top

Gender
The mean elimination half-life of mirtazapine after oral administration ranges from approximately 20–40 hours across age and gender subgroups, with females of all ages exhibiting significantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males). Return to top

Race
There have been no clinical studies to evaluate the effect of race on the pharmacokinetics of Ranitidine. Return to top

Renal Insufficiency
The disposition of mirtazapine was studied in patients with varying degrees of renal function. Elimination of mirtazapine is correlated with creatinine clearance. Total body clearance of mirtazapine was reduced approximately 30% in patients with moderate (Clcr = 11–39 mL/min/1.73 m2) and approximately 50% in patients with severe (Clcr = < 10 mL/min/1.73 m2) renal impairment when compared to normal subjects. Caution is indicated in administering Ranitidine to patients with compromised renal function. Return to top

Hepatic Insufficiency
Following a single 15 mg oral dose of Ranitidine, the oral clearance of mirtazapine was decreased by approximately 30% in hepatically impaired patients compared to subjects with normal hepatic function. Caution is indicated in administering Ranitidine to patients with compromised hepatic function. Return to top