A Novel Pharmacokinetic Bridging Strategy to Support a Change in the Route of Administration for Biologics

Abstract

Determination of appropriate pharmacokinetic end point to bridge different dosing regimens is often a challenge when developing a new route of administration. Trough concentrations (Ctrough) are often considered the most relevant PK end point to predict efficacy (ACR20/DAS28) in the treatment of rheumatoid arthritis for biologics. However, no systematic research has been conducted to evaluate this approach. We developed a novel strategy to predict the most relevant PK variables that may be used to support a change in the route of administration for biological products. Our analysis indicated that matching only Ctrough when switching from intravenous dosing to subcutaneous dosing with decreasing dosing interval may result in a lower treatment response. If only average concentration (Cave) is considered as the relevant variable, our analysis showed that treatment response may be worsened when switching from subcutaneous dosing to intravenous dosing with increasing dosing interval. The study results demonstrated that matching a single pharmacokinetic end point (Ctrough or Cave) may not be sufficient to ensure efficacy when switching between intravenous dosing and subcutaneous dosing. A practical novel pharmacokinetic bridging approach is provided to support a change in the route of administration for biological products.