Background:
Cardiovascular disease has one of the highest mortality rates among all the diseases. Platelets
play an important role in the pathogenesis of cardiovascular diseases. Platelet membrane glycoprotein GPIIb/IIIa
antagonists are the most effective antiplatelet drugs, and pulaimab is one of these. The study aims to promote individual
medication of pulaimab [anti-GPIIb/IIIa F(ab)2 injection] by discovering the pharmacological relationship
among the dose, concentration, and effects. The goal of this study is to establish a population pharmacokineticpharmacodynamic
model to evaluate the antiplatelet effect of intravenous pulaimab injection.
Methods:
Data were collected from 59 healthy subjects who participated in a Phase-I clinical trial. Plasma concentration
was used as the pharmacokinetic index, and platelet aggregation inhibition rate was used as the pharmacodynamic
index. The basic pharmacokinetics model was a two-compartment model, whereas the basic pharmacodynamics
model was a sigmoid-EMAX model with a direct effect. The covariable model was established by a stepwise
method. The final model was verified by a goodness-of-fit method, and predictive performance was assessed by a
Bootstrap (BS) method.
Results:
In the final model, typical population values of the parameters were as follows: central distribution Volume
(V1), 183 L; peripheral distribution Volume (V2), 349 L; Central Clearance (CL), 31 L/h; peripheral clearance(Q),
204 L/h; effect compartment concentration reaching half of the maximum effect (EC50), 0.252 mg/L; maximum
effect value (EMAX), 54.0%; and shape factor (γ), 0.42. In the covariable model, thrombin time had significant
effects on CL and EMAX. Verification by the goodness-of-fit and BS methods showed that the final model was
stable and reliable.
Conclusion:
A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection
that could provide support for the clinical therapeutic regimen.