Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Third communication: correspondence of the idiotype activity and virus neutralization activity of the new monoclonal antibody, regavirumab in rat serum and its pharmacokinetics in rats and monkeys.

TI-23 consists of lyophilized regavirumab (monoclonal antibody C23, MCA C23), a new human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid. The pharmacokinetics of MCA C23 was studied in rats and monkeys, and virus neutralization activity was investigated after intravenous administration of TI-23 in rats. MCA C23 idiotype activity (antigenicity against idiotype antibody) was not affected by heat treatment. The rat serum obtained after injection of TI-23 showed a potent inhibition activity of plaque formation. A good correlation (r = 0.873) was observed between idiotype activity and the inhibition activity of plaque formation in the diluted serum samples. After single or repeated injection of TI-23 to cynomolgus monkeys, the MCA C23 concentration in plasma was determined by an immunological method. 1 h after single injection, 60.8 +/- 5.1 micrograms/ml of MCA C23 was detected in plasma, then the plasma level decreased with an elimination half-life of 20.5 +/- 6.2 days and the AUC value was 18.3 +/- 3.4 mg.h/ml. In the repeated administration experiment (2 mg/kg/week, 5 times), the MCA C23 plasma concentration reached a steady state (74.4 +/- 11.8 micrograms/ml) at 24 h after the fourth injection. The elimination half-life after the final injection was similar to that after the single injection.