Application of a two-analyte integrated population pharmacokinetic model to evaluate the impact of intrinsic and extrinsic factors on the pharmacokinetics of …
D Lu, T Lu, R Shi, L Gibiansky, P Agarwal… - Pharmaceutical …, 2020 - Springer
Pharmaceutical Research, 2020•Springer
Purpose The established two-analyte integrated population pharmacokinetic model was
applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of
polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following
bodyweight-based dosing. Methods Model simulations based on individual empirical Bayes
estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups
on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal …
applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of
polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following
bodyweight-based dosing. Methods Model simulations based on individual empirical Bayes
estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups
on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal …
Purpose
The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing.
Methods
Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance.
Results
No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100–146 kg versus 38–<100 kg, age ≥ 65 years versus <65 years, female versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK.
Conclusions
In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100–146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated.
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