Source: Health Products Regulatory Authority (ZA) Revision Year: 2021 Publisher: RANBAXY PHARMACEUTICALS (PTY) LTD, 14 Lautre Road, Stormill, Ext. 1, Roodepoort, 1724, South Africa
Pharmacotherapeutic group: A.5.7.1 Antihistaminics – other antihistamines for systemic use
ATC code: R06AX28
Rupatadine is a non-sedating, long-acting histamine antagonist, with selective peripheral H1-receptors.
At the recommended dose of 10 mg, the reported onset of the antihistamine activity was at 30 minutes and the effect lasted for 24 hours. Some of the metabolites (desloratadine and its hydroxylated metabolites) have an antihistaminic activity and may contribute to the overall efficacy of rupatadine.
Rupatadine possesses antihistamine properties such as the inhibition of the degranulation of mast cells induced by immunological and non-immunological stimuli, and inhibition of the release of cytokines, particularly of the Tumour Necrosis Factor alpha (TNFa) in human mast cells and monocytes.
Rupatadine shows high H1-receptor affinity and little or no activity on other CNS receptors.
Rupatadine is reported to be rapidly absorbed after oral administration, with a Tmax of approximately 0,75 hours after intake. The mean Cmax was 2,6 ng/ml after a single oral dose of 10 mg. After a dose of 10 mg/day for 7 days, the reported Cmax was 3,8 ng/ml. The plasma concentration exhibited a bi-exponential drop-off with a mean elimination half-life of 5,9 hours.
Intake of food increased the systemic exposure (AUC) to rupatadine by about 23%. The exposure to one of its active metabolites and to the main inactive metabolite was practically the same (reduction of about 5% and 3%, respectively). The time taken to reach the maximum plasma concentration (Tmax) of rupatadine was reported to be delayed by 1 hour. The maximum plasma concentration (Cmax) was not affected by food intake. These differences had no clinical significance.
Rupatadine is reported to be 98% to 99% bound to human plasma proteins.
The main biotransformation pathways of rupatadine identified were different oxidative processes, namely oxidation of the pyridine methyl group to the carboxylic acid, hydroxylation in the 3,5 and 6 positions in the tricyclic ring system and N-dealkylation of the piperadine nitrogen. Conjugates with glucuronic acid were also found. Some of the metabolites retain antihistaminic activity and may partially contribute to the overall efficacy of rupatadine and a long duration of action.
Cytochrome P450 CYP3A4 was identified in vitro as the main isoenzyme responsible for the biotransformation of rupatadine, but other CYP isoenzymes like CYP2C9, CYP2C19 and CYP2D6 are also reported to be involved.
The plasma concentration exhibited a bi-exponential decay, with a mean elimination half-life of 5,9 hours. In a study of excretion in humans (40 mg of 14C-rupatadine), 34,6% of the radioactive medicine administered was recovered in urine and 60,9% in faeces collected over 7 days. Biliary excretion is the most important elimination route for rupatadine.
Rupatadine undergoes considerable pre-systemic metabolism when administered by oral route. The amounts of unaltered active substance found in urine and faeces were insignificant.
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