Poziotinib (HM781-36B): Pharmacokinetics, Applications in the Treatment of Non-Small-Cell Lung Cancer and Dosage

General Description

Poziotinib (HM781-36B) is a novel anticancer drug with pharmacokinetic properties following a two-compartment model of first-order elimination kinetics. It has a half-life of 6.6 hours, a volume of distribution of 164 liters, and an apparent clearance rate of 34.5 liters per hour. This drug reaches peak blood concentrations 1.75 hours after oral administration, unaffected by food intake. In the treatment of Non-Small-Cell Lung Cancer (NSCLC), particularly with EGFR or HER2 exon 20 mutations, Poziotinib (HM781-36B) shows promise by targeting these genetic alterations. The recommended dosage ranges from 12mg to 24mg once daily, with dosing adjustments based on individual tolerability.

Figure 1. Poziotinib (HM781-36B)

Pharmacokinetics

Poziotinib (HM781-36B), a novel anticancer drug, exhibits pharmacokinetic properties consistent with a two-compartment model of first-order elimination kinetics. With a half-life of 6.6 hours, an average volume of distribution of 164 liters, and an average apparent clearance rate of 34.5 liters per hour, Poziotinib (HM781-36B) reaches peak blood concentrations 1.75 hours after oral administration. Importantly, the absorption and blood concentration of Poziotinib (HM781-36B) are not affected by food intake, indicating consistent bioavailability regardless of meal status. Body weight significantly influences Poziotinib (HM781-36B)'s central volume of distribution, highlighting the impact of patient-specific factors on drug disposition. The absorption rate constant is also modulated by food intake, underscoring the importance of dosing conditions in optimizing drug exposure. Despite these influences, other covariates do not substantially alter Poziotinib (HM781-36B)'s pharmacokinetics, emphasizing the robustness of the proposed population model. Overall, the population pharmacokinetic analysis elucidates the predictable behavior of Poziotinib (HM781-36B) across various solid tumor types, offering insights into its systemic disposition and factors affecting drug absorption. By characterizing Poziotinib (HM781-36B)'s pharmacokinetic profile, this study enhances our understanding of its clinical pharmacology and supports informed dosing strategies in cancer patients. ¹

Applications in the treatment of Non-Small-Cell Lung Cancer

Poziotinib (HM781-36B) is a tyrosine kinase inhibitor that has shown promise in the treatment of Non-Small-Cell Lung Cancer, particularly in cases where the cancer has specific genetic mutations. NSCLC patients with EGFR or HER2 exon 20 insertion mutations have limited treatment options, and Poziotinib offers a targeted therapy approach for these individuals. Clinical studies have demonstrated that Poziotinib exhibits efficacy in inhibiting the activity of EGFR and HER2 receptors with exon 20 insertion mutations, which are known to drive the growth of certain NSCLC tumors. As a result, Poziotinib (HM781-36B) has shown potential in providing meaningful clinical benefit for patients with this specific genetic alteration. In trials, Poziotinib (HM781-36B) has exhibited promising anti-tumor activity and has been well-tolerated in NSCLC patients with these mutations. This suggests its potential as a valuable treatment option in this subset of NSCLC. It's important to note that the use of Poziotinib (HM781-36B) in NSCLC is still under investigation, and its application may be subject to further refinement pending the results of ongoing clinical research. Patients considering Poziotinib (HM781-36B) treatment should consult with their healthcare provider to determine if it is a suitable option based on their individual medical history and genetic profile. ²

Dosage

Poziotinib (HM781-36B) is a medication used in the treatment of certain types of cancer, and its dosage and administration are crucial for its effectiveness. The maximum tolerated dose of Poziotinib is 24mg once daily, with a schedule of two weeks on and one week off, or 18mg once daily continuously. The standard dosing regimen is 16mg once daily (approximately equivalent to 17mg of Poziotinib (HM781-36B) hydrochloride, with a conversion ratio of 1:1.07), to be taken with or without food on a continuous basis. In cases where adverse reactions are intolerable, the dosage can be reduced to 14mg or even 12mg once daily. For those considering an intermittent dosing approach, Poziotinib (HM781-36B) can be taken at 24mg for three days, followed by a one-day break. In instances of intolerable adverse reactions, the dosage can be reduced to 18mg for three days, followed by a one-day break. It's important to consult a healthcare professional for personalized dosing recommendations based on individual health circumstances. ³

Reference

1. Noh YH, Lim HS, Jung JA, Song TH, Bae KS. Population pharmacokinetics of HM781-36 (poziotinib), pan-human EGF receptor (HER) inhibitor, and its two metabolites in patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2015;75(1):97-109.

2. Le X, Cornelissen R, Garassino M, et al. Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial. J Clin Oncol. 2022;40(7):710-718.

3. Poziotinib (Pending FDA Approval). Medscape.