PHARMACOKINETICS OF A NEW HUMAN MONOCLONAL-ANTIBODY AGAINST CYTOMEGALOVIRUS .3. 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, MC A 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 antibo dy) was not affected by heat treatment. The rat serum obtained after i njection of TI-23 showed a potent inhibition activity of plaque format ion. A good correlation (r = 0.873) was observed between idiotype acti vity and the inhibition activity of plaque formation in the diluted se rum samples. After single or repeated injection of TI-23 to cynomolgus monkeys, the MCA C23 concentration in plasma was determined by an imm unological method. 1 h after single injection, 60.8 +/- 5.1 mu g/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 s tate (74.4 +/- 11.8 mu g/ml) at 24 h after the fourth injection. The e limination half-life after the final injection was similar to that aft er the single injection.