Pharmacokinetics of a new human monoclonal antibody against cytomegalovirus. Second communication: distribution and elimination of the new monoclonal antibody, regavirumab after repeated administration in rats, and placental transfer and milk-passage study after single administration to pregnant and lactating rats.

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 tissue distribution or pharmacokinetics of MCA C23 was investigated after repeated administration in male rats and single administration in pregnant and lactating rats. Radioactivity and MCA C23 idiotype activity (antigenicity against idiotype antibody) in plasma increased with weekly injections during repeated administration of 125I-labeled TI-23 (2 mg/kg/week). After the fourth injection, the plasma radioactivity concentration reached a steady state and the elimination half-life was determined to be 11.2 days. No significant difference was observed between the radioactivity and the idiotype activity in plasma, indicating that MCA C23 was stable in vivo. The plasma concentration curve after repeated administration corresponded with that simulated by the pharmacokinetic parameters obtained previously and the minimum steady state concentration (Css-min) at 168 h after repeated administration was about 33 micrograms eq. of MCA C23/ml. Trans-placental tissue distribution of radioactivity was investigated after single administration of 125I-TI-23 to 19-day pregnant rats. About 12% of the dose was transferred to the fetus and the idiotype activity remained in fetal tissues at 24 h after injection. In lactating rats, some radioactivity was secreted into the milk and the ratio of milk to plasma radioactivity reached 0.28 after a single administration of 125I-TI-23. Some MCA C23 idiotype activity was observed in the milk.