Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs

Naoya Matsumura; Shun Hayashi; Yoshiyuki Akiyama; Asami Ono; Satoko Funaki; Naomi Tamura; Takahiro Kimoto; Maiko Jiko; Yuka Haruna; Akiko Sarashina; Masahiro Ishida; Kotaro Nishiyama; Masahiro Fushimi; Yukiko Kojima; Kazuhiro Yoneda; Misato Nakanishi; Soonih Kim; Takuya Fujita; Kiyohiko Sugano

doi:10.1016/j.xphs.2019.12.009

Prediction Characteristics of Oral Absorption Simulation Software Evaluated Using Structurally Diverse Low-Solubility Drugs

J Pharm Sci. 2020 Mar;109(3):1403-1416. doi: 10.1016/j.xphs.2019.12.009. Epub 2019 Dec 18.

Authors

Naoya Matsumura¹, Shun Hayashi², Yoshiyuki Akiyama³, Asami Ono⁴, Satoko Funaki⁵, Naomi Tamura⁵, Takahiro Kimoto³, Maiko Jiko⁶, Yuka Haruna⁶, Akiko Sarashina⁷, Masahiro Ishida⁷, Kotaro Nishiyama⁸, Masahiro Fushimi⁹, Yukiko Kojima⁹, Kazuhiro Yoneda¹⁰, Misato Nakanishi¹⁰, Soonih Kim¹⁰, Takuya Fujita¹¹, Kiyohiko Sugano¹²

Affiliations

¹ Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan. Electronic address: na.matsumura@ono.co.jp.
² Preclinical Research Unit, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan.
³ Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
⁴ Laboratory for Chemistry, Manufacturing and Control Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni, Shizuoka 410-2321, Japan.
⁵ Drug Metabolism & Pharmacokinetics, Research Laboratory for Development, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
⁶ Medical Analysis Research Department, Towa Pharmaceutical Co., Ltd., 134 Chudoji Minami-machi, Shimogyo-ku, Kyoto 600-8813, Japan.
⁷ Clinical PK/PD Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
⁸ Pharmacokinetics and Non-Clinical Safety Department, Nippon Boehringer Ingelheim Co., Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
⁹ Biological Research Department, Sawai Pharmaceutical Co., Ltd., 5-2-30, Miyahara, Yodogawa-ku, Osaka 532-0003, Japan.
¹⁰ Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
¹¹ Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan.
¹² Molecular Pharmaceutics Laboratory, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan.

PMID: 31863733
DOI: 10.1016/j.xphs.2019.12.009

Abstract

The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans. As commercial software products, GastroPlus™ and Simcyp® were used. In addition, the gastrointestinal unified theoretical framework, a simple and publicly accessible model, was used as a benchmark. The Fa prediction characteristics for a total of 96 clinical Fa data of 27 model drugs were systematically evaluated using the default settings of each software product. The molecular weight, dissociation constant, octanol-water partition coefficient, solubility in biorelevant media, dose, and particle size of model drugs were used as input data. Although the same input parameters were used, GastroPlus™, Simcyp®, and the gastrointestinal unified theoretical framework showed different Fa prediction characteristics depending on the rate-limiting steps of oral drug absorption. The results of the present study would be of great help for the overall progression of physiologically based absorption models.

Keywords: dissolution; oral absorption; permeability; simulation; solubility.

Publication types

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

MeSH terms

Administration, Oral
Computer Simulation
Humans
Intestinal Absorption*
Models, Biological
Permeability
Pharmaceutical Preparations*
Software
Solubility

Substances

Pharmaceutical Preparations