Prediction of Human Serum Concentration-Time Profiles of Golimumab and Ustekinumab Using Pharmacokinetic Data From Common Marmosets With Assessment of Anti-Drug Antibodies.

In a previous study, retrospective predictions of human serum concentration-time profiles for three therapeutic monoclonal antibodies (mAbs) with linear pharmacokinetics were performed using allometric scaling in common marmosets and achieved favorable predictability. To generalize this method, in the present study, golimumab and ustekinumab, which exhibit linear pharmacokinetics, were repeatedly administered to marmosets. Additionally, the immunogenicity of these mAbs in common marmosets was evaluated. Golimumab and ustekinumab were administered in four repeated doses. Following the initial administration, the scaling exponents of the two mAbs were calculated, and the average scaling exponents of the five mAbs were used for the predictions. Furthermore, serum anti-ustekinumab and anti-golimumab antibodies were evaluated following the repeated-dose administration. Human serum concentration-time curves of golimumab and ustekinumab were predicted using the average scaling exponents of the five mAbs. Although the predictability of the golimumab elimination rate was slightly inferior, ustekinumab showed excellent prediction performance. Low levels of anti-ustekinumab antibodies were detected in the serum when the serum ustekinumab levels were considered to have completely diminished. Furthermore, serum anti-golimumab antibodies were negligible during the experimental period. We identified provisional optimal scaling exponents for predicting human PK and found minimal anti-drug antibody formation. As the cost of acquiring and maintaining cynomolgus monkeys is increasing, pharmacokinetic data of marmosets is expected to encourage the potential use of these small non-human primates as an alternative model.