Nudoxa PEG Mechanism of Action

Pharmacotherapeutic group: Anthracyclines and related substances. ATC code: L01DB01.
Pharmacology: Pharmacodynamics: Mechanism of action: The active ingredient of doxorubicin hydrochloride liposome injection is doxorubicin hydrochloride. The mechanism of action of doxorubicin hydrochloride is thought to be related to its ability to bind DNA and inhibit nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations.
Pharmacokinetic: The pharmacokinetic parameters for total doxorubicin following a single dose of doxorubicin hydrochloride liposome injection infused over 30 minutes are presented in Table 1. (See Table 1.)

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Doxorubicin hydrochloride liposome injection displayed linear pharmacokinetics over the range of 10 to 20 mg/m². Relative to doxorubicin hydrochloride liposome injection doses at or below 20 mg/m², the pharmacokinetics of total doxorubicin following a 50 mg/m² doxorubicin hydrochloride liposome injection dose are nonlinear. At this dose, the elimination half-life of doxorubicin hydrochloride liposome injection is longer and the clearance lower compared to a 20 mg/m² dose.
Distribution: Direct measurement of liposomal doxorubicin shows that at least 90% of the drug (the assay used cannot quantify less than 5-10% free doxorubicin) remains liposome-encapsulated during circulation.
In contrast to doxorubicin, which displays a large volume of distribution (range 700 to 1,100 L/m²), the small steady state volume of distribution of liposomal doxorubicin suggests that doxorubicin hydrochloride liposome injection is largely confined to vascular fluid. Doxorubicin becomes available after the liposomes are extravasated. Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined; the plasma protein binding of doxorubicin is approximately 70%.
Metabolism: Doxorubicinol, the major metabolite of doxorubicin, was detected at concentrations of 0.8 to 26.2 ng/mL in the plasma of patients who received 10 or 20 mg/m² doxorubicin hydrochloride liposome injection.
Elimination: The plasma clearance of total doxorubicin from doxorubicin hydrochloride liposome injection was 0.041 L/h/m² at a dose of 20 mg/m². Following administration of doxorubicin hydrochloride, the plasma clearance of doxorubicin is 24 to 35 L/h/m².