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Clinical Trial
. 2015 Jan;75(1):97-109.
doi: 10.1007/s00280-014-2621-7. Epub 2014 Nov 7.

Population pharmacokinetics of HM781-36 (poziotinib), pan-human EGF receptor (HER) inhibitor, and its two metabolites in patients with advanced solid malignancies

Yook-Hwan Noh  1 , Hyeong-Seok Lim, Jin-A Jung, Tae Hun Song, Kyun-Seop Bae
Affiliations
Clinical Trial

Population pharmacokinetics of HM781-36 (poziotinib), pan-human EGF receptor (HER) inhibitor, and its two metabolites in patients with advanced solid malignancies

Yook-Hwan Noh et al. Cancer Chemother Pharmacol. 2015 Jan.

Abstract

Purpose: To develop a population pharmacokinetic (PK) model for HM781-36 (poziotinib) and its metabolites in cancer patients.

Methods: Blood samples were collected from three phase I studies in which fifty-two patients received oral HM781-36B tablets (0.5-32 mg) once daily for 2 weeks, and another 20 patients received oral HM781-36B tablets (12, 16, 18, 24 mg) in fasting (12 patients) or fed (eight patients) state once daily for 4 weeks. Nonlinear mixed effect modeling was employed to develop the population pharmacokinetic model.

Results: HM781-36 PK was ascribed to a two-compartment model and HM781-36-M1/-M2 PK to one-compartment model. HM781-36 oral absorption was characterized by first-order input (absorption rate constant: 1.45 ± 0.23 h⁻¹). The central volume of distribution (185 ± 12.7 L) was influenced significantly by body weight. The absorption rate constant was influenced by food. The typical HM781-36 apparent clearance was 34.5 L/h (29.4 %CV), with an apparent peripheral volume of distribution of 164 L (53.5 %CV). Other covariates did not significantly further explain the PKs of HM781-36.

Conclusions: The proposed model suggests that HM781-36 PKs are consistent across most solid tumor types, and that the absorption process of HM781-36 is affected by the fed state before dosing. HM781-36 PKs are not complicated by patient factors, other than body weight.

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