首页|Potential pharmacokinetic interaction between orally administered drug and osmotically active excipients in pediatric polypharmacy

Potential pharmacokinetic interaction between orally administered drug and osmotically active excipients in pediatric polypharmacy

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  • NSTL
  • Elsevier
Poorly absorbable sugar alcohols (e.g., mannitol, sorbitol, and maltitol) are the excipients frequently contained in pediatric dosage forms. Due to their osmotically active properties, certain amount of sugar alcohols reportedly reduces oral bioavailability of concomitant drugs. This fact implies the possible pharmacokinetic interaction between orally administered drug and sugar alcohols which are present in other concomitant medications. The purpose of this study was to identify the possibility and likeliness of the osmotically active excipient-induced pharmacokinetic interaction in pediatric polypharmacy. Previously developed in silico model that captured the osmotic effect of sugar alcohols in adults was expanded to pediatric population. This mathematical model successfully explained the impaired bioavailability of lamivudine by the co-administered sorbitol in other dosage forms. In the meantime, sugar alcohol contents in marketed pediatric dosage forms were investigated by reverse engineering technology. Considering the critical administration dose of sugar alcohols estimated by in silico model, it was revealed that 25 out of 153 pediatric dosage forms were identified as possible perpetrators even under the approved administration and dosage in Japan. This study shed light on the potential pharmacokinetic interaction that cannot be dismissed throughout the pediatric pharmaceutical dosage form design and development.

BioavailabilityPediatricsModeling and simulationPolypharmacyOsmotic effectExcipient(s)

Matsui, Kazuki、Nakagawa, Tomoya、Okumura, Tomonori、Yamane, Miki、Tokunaga, Yuji、Yokota, Shoji

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Sawai Pharmaceut Co Ltd, Pharmacokinet Grp, Biol Res Dept, Res & Dev Div, Osaka, Japan

Sawai Pharmaceut Co Ltd, Res & Dev Div, Formulat Grp 4, Pharmaceut Dev Dept, Osaka, Japan

Sawai Pharmaceut Co Ltd, Res & Dev Div, New Prod Planning Dept, Planning Grp, Osaka, Japan

Sawai Pharmaceut Co Ltd, Res & Dev Div, Osaka, Japan

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2021

10.1016/j.ejps.2021.105934

European journal of pharmaceutical sciences

European journal of pharmaceutical sciences

ISTP
ISSN：0928-0987
年,卷(期)：2021.165
  • 54