**8. Pharmacokinetics and –Dynamics**

In preparation of clinical trials, several preclinical toxicology and pharmacokinetic studies have been carried out in mice and non-human primates [143–147]. These studies confirmed safety of intravenous injection of up to 10<sup>8</sup> and 4 <sup>×</sup> <sup>10</sup><sup>8</sup> TCID50/kg oncolytic MeV in IFNAR−/<sup>−</sup> CD46Ge and squirrel monkeys, respectively. Further, intraventricular injection of oncolytic MeV into the cerebrospinal fluid of IFNAR−/<sup>−</sup> CD46Ge mice [147] and intrahepatic injection of prodrug convertase-armed oncolytic MeV in IFNAR−/<sup>−</sup> CD46Ge mice and rhesus macaques [146] were tolerated. Depending on the model, different pharmacokinetics and dose–response relationships were observed. Notably, despite detection of viral RNA, no significant shedding of infectious virus was reported.

This holds true in clinical settings. Saliva and urine samples were free of infectious virus after i.p. administration of MV-CEA in ovarian cancer patients [74]. Up to 10<sup>9</sup> TCID<sup>50</sup> i.p. and 10<sup>11</sup> TCID<sup>50</sup> i.v. have been administered with manageable side effects [75,122]. The available clinical data also suggest a dose–response relationship, with higher doses associated with more favorable outcome.
