Iritero Mechanism of Action

Pharmacology: Pharmacodynamics: Therapeutic class: Irinotecan Hydrochloride is an antineoplastic agent of the topoisomerase I inhibitor class. Irinotecan is a semisynthetic derivative of Camptothecin, an alkaloid extract from plants such as Camptotheca acuminata, or is chemically synthesized.
Mechanism of action: Irinotecan and its active metabolite SN-38 bind to the topoisomerase I - DNA complex and prevent re-ligation of these single-strand breaks. Current research suggests that the cytotoxicity of Irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38.
Irinotecan serves as a water-soluble precursor of the lipophilic metabolite SN-38. SN-38 is formed from Irinotecan by carboxylesterases-mediated cleavage of the Carbamate bond between the Camptothecin moiety and the dipiperidino side chain. SN-38 is approximately 1000 times as potent as Irinotecan as an inhibitor of topoisomerase I. The precise contribution of SN-38 to the activity of Irinotecan is thus known. Both Irinotecan and SN-38 exist in an active lactone form and an inactive hydroxy acid anion form. A pH-dependent equilibrium exist between the two forms such that an acid pH promotes the formation of the lactone, while a more basic pH favors the hydroxy acid anion form.
Pharmacokinetics in special populations: Geriatric: No differences in the pharmacokinetics of Irinotecan, SN-38, and SN-38 glucuronide in patients < 65 years of age compared with patients ≥ 65 years of age.
Gender: The pharmacokinetics of Irinotecan do not appear to be influenced by gender.
Race: The influence of race on the pharmacokinetics of Irinotecan has not been evaluated.
Hepatic insufficiency: Irinotecan clearance is diminished in patients with hepatic dysfunction while relative exposure to the active metabolite SN-38 is increased. The magnitude of these effects is proportional to the degree of liver impairment as measured by elevations in serum total bilirubin and transaminase concentrations.
Renal insufficiency: The influence of renal insufficiency on the pharmacokinetics of Irinotecan has not been evaluated.