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

• Preclinical studies in rats show rapid absorption and elimination of caffeine with no effect from co-administered model mAb. • Caffeine does not affect PK profiles and SQ bioavailability of the model mAb. • SQ injection of caffeine at the tested dose levels shows no safety concern. • Current studies ensure further development of caffeine as a viscosity reducing excipient for high concentration mAb formulations. 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. [ABSTRACT FROM AUTHOR]