Pharmacokinetics of an intracerebroventricularly administered antibody in rats

MAbs. 2017 Oct;9(7):1210-1215. doi: 10.1080/19420862.2017.1345834. Epub 2017 Jul 6.

Abstract

The pharmacokinetics (PK) of an antibody in the brain and the spinal cord is insufficiently understood, which is an obstacle to the discovery of antibody drugs that target diseases in the central nervous system. In this study, we focused on the elimination of IgG from cerebrospinal fluid (CSF) circulating in the brain and the spinal cord in rats, and, to evaluate the influence of CSF bulk flow on the clearance of IgG, also examined the PK of inulin in CSF. To monitor their concentrations in CSF, IgG and inulin were co-administered into the lateral ventricle via a catheter, and CSF was collected from the cisterna magna via another catheter time-sequentially. Blood was also obtained from the same individuals, and the concentrations of IgG and inulin in CSF and plasma were measured. The results revealed that PK parameters of IgG were similar to those of inulin; half-life and clearance of IgG were 47.0 ± 6.49 min and 29.0 ± 15.2 mL/day/kg, and those of inulin were 52.8 ± 25.4 min and 29.0 ± 13.3 mL/day/kg. Moreover, deconvolution analysis indicated that all of the IgG administered in the lateral ventricle was transferred to plasma from CSF within 24 hours. This study demonstrated that IgG in CSF was eliminated by bulk flow and transferred totally to blood circulation.

Keywords: Antibody; CSF; brain; bulk flow; inulin; pharmacokinetics; sequential sampling.

MeSH terms

  • Animals
  • Female
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / cerebrospinal fluid
  • Immunoglobulin G / pharmacology
  • Injections, Intraventricular
  • Rats

Substances

  • Immunoglobulin G