Preclinical Pharmacokinetic Study on Caffeine as an Excipient for Monoclonal Antibody Formulations

Yuhong Zeng; Subhashchandra Naik; Timothy Tran; Philip Wuthrich; Neal Muni; Robert P Mahoney

doi:10.1016/j.xphs.2023.07.023

Preclinical Pharmacokinetic Study on Caffeine as an Excipient for Monoclonal Antibody Formulations

J Pharm Sci. 2023 Nov;112(11):2933-2937. doi: 10.1016/j.xphs.2023.07.023. Epub 2023 Jul 28.

Authors

Yuhong Zeng¹, Subhashchandra Naik², Timothy Tran², Philip Wuthrich², Neal Muni², Robert P Mahoney²

Affiliations

¹ Comera Life Sciences, Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, USA. Electronic address: yzeng@comerals.com.
² Comera Life Sciences, Inc., 12 Gill Street Suite 4650, Woburn, MA 01801, USA.

PMID: 37517525
DOI: 10.1016/j.xphs.2023.07.023

Abstract

Caffeine is a novel excipient that effectively reduces viscosity of high concentration mAb formulations intended for subcutaneous (SQ) delivery. Two preclinical studies were conducted in rats to evaluate pharmacokinetic (PK) parameters of caffeine as well as its effects on the PK profile of a model mAb, namely ipilimumab. Results show that SQ absorption and elimination of caffeine was rapid, with the average T_max of 0.4 h and T_1/2 of 1.6 h, administered with or without ipilimumab. Furthermore, caffeine did not affect ipilimumab SQ PK profiles. Independent of caffeine concentration, ipilimumab serum T_1/2 was between 2 and 3 days, T_max was between 3 and 4 days and SQ bioavailability was about 64%. In addition, SQ injection of caffeine at different dose levels showed no irritation at the injection site or adverse effects. Results from the current PK studies warrant further development of caffeine as a viscosity reducing excipient for mAb SQ formulations.

Keywords: Caffeine; Excipient; Monoclonal antibody; Preclinical pharmacokinetics; Subcutaneous injection.