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Pharmaceuticals
Volume 14
Issue 9
10.3390/ph14090927
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Article

Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC

by
Agustos Cetin Ozbey
1,
David Combarel
1,2,
Vianney Poinsignon
1,
Christine Lovera
3,
Esma Saada
3,
Olivier Mir
4 and
Angelo Paci
1,2,*
1
Service de Pharmacologie, Département de Biologie et Pathologie Médicales, Gustave Roussy, Université Paris-Saclay, F-94800 Villejuif, France
2
Service de Pharmacocinétique, Faculté de Pharmacie, Université Paris-Saclay, F-92296 Chatenay-Malabry, France
3
Centre Antoine Lacassagne, Délégation à la Recherche Clinique, F-06189 Nice, France
4
Département de Soins Ambulatoire, Gustave Roussy, F-94800 Villejuif, France
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2021, 14(9), 927; https://doi.org/10.3390/ph14090927
Submission received: 14 July 2021 / Revised: 5 September 2021 / Accepted: 9 September 2021 / Published: 15 September 2021
(This article belongs to the Special Issue Precision Medicine in Oncology: Controlling the Pharmacokinetics Variability)
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Abstract

Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L−1. However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient’s AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L−1 was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments.
Keywords: cancer; tyrosine kinase inhibitors; population pharmacokinetics; therapeutic drug monitoring (TDM) cancer; tyrosine kinase inhibitors; population pharmacokinetics; therapeutic drug monitoring (TDM)

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MDPI and ACS Style

Ozbey, A.C.; Combarel, D.; Poinsignon, V.; Lovera, C.; Saada, E.; Mir, O.; Paci, A. Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC. Pharmaceuticals 2021, 14, 927. https://doi.org/10.3390/ph14090927

AMA Style

Ozbey AC, Combarel D, Poinsignon V, Lovera C, Saada E, Mir O, Paci A. Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC. Pharmaceuticals. 2021; 14(9):927. https://doi.org/10.3390/ph14090927

Chicago/Turabian Style

Ozbey, Agustos Cetin, David Combarel, Vianney Poinsignon, Christine Lovera, Esma Saada, Olivier Mir, and Angelo Paci. 2021. "Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC" Pharmaceuticals 14, no. 9: 927. https://doi.org/10.3390/ph14090927

APA Style

Ozbey, A. C., Combarel, D., Poinsignon, V., Lovera, C., Saada, E., Mir, O., & Paci, A. (2021). Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC. Pharmaceuticals, 14(9), 927. https://doi.org/10.3390/ph14090927

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