Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

12.2      Pharmacodynamics
Lutetium Lu 177 vipivotide tetraxetan exposure-efficacy relationships and the time course of pharmacodynamic response have not been fully characterized.
Cardiac Electrophysiology
At the recommended dosage, PLUVICTO does not cause large mean increases (> 20 ms) in the QTc interval.

Pharmacokinetic Properties

12.3      Pharmacokinetics
Pharmacokinetics of lutetium Lu 177 vipivotide tetraxetan are expressed as geometric mean (geometric mean coefficient of variation) unless otherwise specified.
The blood lutetium Lu 177 vipivotide tetraxetan area under the curve (AUC) is 52.3 ng.h/mL (31.4%) and the maximum blood concentration is 6.58 ng/mL (43.5%) at the recommended dosage.
Distribution
Lutetium Lu 177 vipivotide tetraxetan volume of distribution is 123 L (78.1%).
Within 2.5 hours of administration, lutetium Lu 177 vipivotide tetraxetan distributes to gastrointestinal tract, liver, lungs, kidneys, heart wall, bone marrow, and salivary glands.
Vipivotide tetraxetan and non-radioactive lutetium vipivotide tetraxetan are 60% to 70% bound to human plasma proteins.
Elimination
The lutetium Lu 177 vipivotide tetraxetan geometric mean terminal elimination half-life is 41.6 hours (68.8%) and the clearance (CL) is 2.04 L/h (31.5%).
Excretion
Lutetium Lu 177 vipivotide tetraxetan is primarily eliminated renally.
PLU API APR23 V1.0                                                               USPI October 2022 Specific Populations
Exposure (AUC) of lutetium Lu 177 vipivotide tetraxetan increased with decreasing creatinine clearance (CLcr). The effect of baseline CLcr < 54 mL/min on lutetium Lu 177 vipivotide tetraxetan pharmacokinetics has not been studied.
Drug Interaction Studies
In Vitro Studies
CYP450 enzymes: Vipivotide tetraxetan is not a substrate of cytochrome P450 (CYP450) enzymes. Vipivotide tetraxetan did not induce CYP1A2, 2B6 or 3A4; and did not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A in vitro.
Transporters: Vipivotide tetraxetan is not a substrate of BCRP, P-gp, MATE1, MATE2-K, OAT1, OAT3 or OCT2.
Vipivotide tetraxetan did not inhibit BCRP, P-gp, MATE1, MATE2-K, OAT1, OAT3, OATP1B1, OATP1B3, OCT1 or OCT2 in vitro.