Antiplatelet Effect of a Pulaimab [Anti-GPIIb/IIIa F(ab)2 Injection] Evaluated by a Population Pharmacokinetic-pharmacodynamic Model
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Current drug metabolism - 20(2019), 13 vom: 27., Seite 1060-1072 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Ya-Ou [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.07.2020 Date Revised 10.07.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1389200220666191122120238 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM303579927 |
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| 245 | 1 | 0 | |a Antiplatelet Effect of a Pulaimab [Anti-GPIIb/IIIa F(ab)2 Injection] Evaluated by a Population Pharmacokinetic-pharmacodynamic Model |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection that could provide support for the clinical therapeutic regimen | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chinese healthy subjects | |
| 650 | 4 | |a antiplatelet | |
| 650 | 4 | |a model | |
| 650 | 4 | |a populationpharmacodynamics | |
| 650 | 4 | |a population pharmacokinetics | |
| 650 | 4 | |a pulaimab [anti-GPIIb/IIIa F(ab)2 injection]. | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Platelet Aggregation Inhibitors |2 NLM | |
| 650 | 7 | |a Platelet Glycoprotein GPIIb-IIIa Complex |2 NLM | |
| 700 | 1 | |a Wang, Zi-Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Chao-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Xian-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Chang-Geng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yi-Min |e verfasserin |4 aut | |
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