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Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application.
J Pharm Sci. 2021 05; 110(5):2301-2310.JP

Abstract

In this study, we aimed to develop and qualify a PBPK model for scalp application using two drugs with marked differences in physicochemical properties and PK profiles. The parameters related to scalp physiology, drug PK, and formulations were incorporated into a Multi-Phase and Multi-Layer (MPML) Mechanistic Dermal Absorption (MechDermA) model within the Simcyp® Simulator V17. The finasteride PBPK model was linked to its effect on dihydrotestosterone (DHT) levels in plasma and scalp using an indirect response model. Predicted PK (and PD for finasteride) profiles and parameters were compared against the clinically reported data and justified by visual predictive checks and two-fold error criteria for model verification. The PBPK/PD model for finasteride reasonably demonstrated an ability to predict its respective PK and PD profiles, and parameters following scalp application under various clinical scenarios. Using the same scalp physiological input parameters, the minoxidil PBPK model was then developed and satisfactorily qualified with independent clinical datasets. Collectively, these results suggested that the established PBPK model may have broader utility for other topical formulations intended for scalp application.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ngampanya A
Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand.
Udomnilobol U
Chulalongkorn University Drug Discovery and Drug Development Research Center (Chula4DR), Chulalongkorn University, Bangkok, Thailand.
Sermsappasuk P
Faculty of Pharmaceutical Sciences, Department of Pharmacy Practice, Naresuan University, Phitsanulok, Thailand.
Pornputtapong N
Faculty of Pharmaceutical Sciences, Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand.
Ongpipattanakul B
Faculty of Pharmaceutical Sciences, Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand.
Patel N
Certara UK Limited (Simcyp Division), Level 2 - Acero, 1 Concourse Way, Sheffield, United Kingdom.
Jianmongkol S
Faculty of Pharmaceutical Sciences, Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand. Electronic address: suree.j@pharm.chula.ac.th.
Prueksaritanont T
Chulalongkorn University Drug Discovery and Drug Development Research Center (Chula4DR), Chulalongkorn University, Bangkok, Thailand. Electronic address: thomayant.p@pharm.chula.ac.th.

MeSH

FinasterideMinoxidilModels, BiologicalScalp

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33609522

Citation

Ngampanya, Arpar, et al. "Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application." Journal of Pharmaceutical Sciences, vol. 110, no. 5, 2021, pp. 2301-2310.
Ngampanya A, Udomnilobol U, Sermsappasuk P, et al. Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application. J Pharm Sci. 2021;110(5):2301-2310.
Ngampanya, A., Udomnilobol, U., Sermsappasuk, P., Pornputtapong, N., Ongpipattanakul, B., Patel, N., Jianmongkol, S., & Prueksaritanont, T. (2021). Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application. Journal of Pharmaceutical Sciences, 110(5), 2301-2310. https://doi.org/10.1016/j.xphs.2021.02.016
Ngampanya A, et al. Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application. J Pharm Sci. 2021;110(5):2301-2310. PubMed PMID: 33609522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application. AU - Ngampanya,Arpar, AU - Udomnilobol,Udomsak, AU - Sermsappasuk,Pakawadee, AU - Pornputtapong,Natapol, AU - Ongpipattanakul,Boonsri, AU - Patel,Nikunjkumar, AU - Jianmongkol,Suree, AU - Prueksaritanont,Thomayant, Y1 - 2021/02/18/ PY - 2020/12/02/received PY - 2021/02/01/revised PY - 2021/02/08/accepted PY - 2021/2/21/pubmed PY - 2021/6/22/medline PY - 2021/2/20/entrez KW - Absorption, Distribution, Metabolism, and Excretion (ADME) KW - Physiologically Based Pharmacokinetic (PBPK) modeling KW - SimCyp PBPK modeling SP - 2301 EP - 2310 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 110 IS - 5 N2 - In this study, we aimed to develop and qualify a PBPK model for scalp application using two drugs with marked differences in physicochemical properties and PK profiles. The parameters related to scalp physiology, drug PK, and formulations were incorporated into a Multi-Phase and Multi-Layer (MPML) Mechanistic Dermal Absorption (MechDermA) model within the Simcyp® Simulator V17. The finasteride PBPK model was linked to its effect on dihydrotestosterone (DHT) levels in plasma and scalp using an indirect response model. Predicted PK (and PD for finasteride) profiles and parameters were compared against the clinically reported data and justified by visual predictive checks and two-fold error criteria for model verification. The PBPK/PD model for finasteride reasonably demonstrated an ability to predict its respective PK and PD profiles, and parameters following scalp application under various clinical scenarios. Using the same scalp physiological input parameters, the minoxidil PBPK model was then developed and satisfactorily qualified with independent clinical datasets. Collectively, these results suggested that the established PBPK model may have broader utility for other topical formulations intended for scalp application. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/33609522/Development_and_Qualification_of_a_Physiologically_Based_Pharmacokinetic_Model_of_Finasteride_and_Minoxidil_Following_Scalp_Application_ DB - PRIME DP - Unbound Medicine ER -
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