Suction
Montelukast quickly and almost completely absorbed after ingestion. In adults, when taking fasting tablets coated with a film coat, 10 mg maximum concentration in the blood plasma (Cmax) is achieved in 3 hours. The average bioavailability with oral administration is 64%. Food intake does not affect Cmax in blood plasma and the bioavailability of the drug.
Distribution
Montelukast binds to plasma proteins more than 99%. The volume distribution of Montelukast in a state of equilibrium concentration averages 8-11 liters. Studies performed on rats with radiolabeled Montelukast indicate a minimal penetration through the blood-brain barrier. In addition, the concentration of labeled Montelukast 24 hours after administration was minimal in all other tissues.
Metabolism
Montelukast is actively metabolized. When studying therapeutic doses in a state of equilibrium concentration in blood plasma in adults and children, the concentration of metabolites of montelukast is not determined.
Research in vitro using human liver microsomes showed that cytochrome P450 isoenzymes CYP: ZA4, 2A6, 2C8 and 2C9 are involved in the metabolism of montelukast. According to further research conducted by in vitro in microsomes of human liver, the therapeutic concentration of montelukast in blood plasma does not inhibit cytochrome P450 isoenzymes CYP: ZA4, 2C9, 1A2, 2A6, 2C19 and 2D6. Excretion
Plasma clearance of montelukast in healthy adults is an average of 45 ml / min. After ingestion of radioactively labeled montelukast, 86% of its quantity is excreted through the intestine within 5 days and less than 0.2% by the kidneys, which confirms that montelukast and its metabolites are excreted almost exclusively with bile. The half-life of montelukast in young healthy adults ranges from 2.7 to 5.5 hours. The pharmacokinetics of montelukast retains a practically linear character when administered in doses over 50 mg. When taking montelukast in the morning and evening hours, there is no difference in pharmacokinetics. When receiving 10 mg of montelukast, a moderate (about 14%) cumulation of the active substance in the blood plasma is observed once a day.
Peculiarities of pharmacokinetics in different patient groups
Floor
The pharmacokinetics of montelukast in women and men is similar.
Elderly patients
With a single oral administration of 10 mg montelukast, the pharmacokinetic profile and bioavailability are similar in elderly patients and young patients. The half-life of montelukast from blood plasma is somewhat greater in elderly patients. Correction of the dose of the drug in elderly patients is not required.
Race
There were no differences in clinically significant pharmacokinetic effects in patients of different races.
Liver failure
In patients with hepatic insufficiency of mild and moderate severity and clinical manifestations of cirrhosis, a decrease in montelukast metabolism was noted, accompanied by an increase in the area under the pharmacokinetic curve "concentration-time" (AUC) approximately 41% after a single dose of 10 mg. The half-life of montelukast in these patients is slightly increased (mean half-life is 7.4 hours). Changes in the dose of montelukast for patients with mild to moderate hepatic insufficiency are not required. There is no data on the character of the pharmacokinetics of montelukast in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale).
Renal insufficiency
Because the montelukast and its metabolites are not excreted through the kidneys, pharmacokinetics of montelukast in patients with renal insufficiency has not been evaluated. A dose adjustment for this group of patients is not required.