Transport of desglycinamide-arginine vasopressin across the blood-brain barrier in rats as evaluated by the unit impulse response methodology.

The pharmacokinetic characteristics of desglycinamide-arginine vasopressin (DGAVP) with respect to its transport across the blood-brain barrier (BBB) were studied with the use of serial CSF sampling in an individual animal and the unit impulse response methodology. Transport rate is determined as BBB clearance, the volume of plasma per unit time cleared of the peptide by BBB transport, and the extent of transport as the percentage of the administered dose transported into the central nervous system. Plasma kinetics of DGAVP were shown to be linear within the dose range studied (50-150 micrograms), plasma mean residence time (MRT) being 18 +/- 4 min (mean +/- SE; n = 9). Elimination of DGAVP from CSF after icv administration was linear, with an MRT of 10 +/- 1 min (n = 9). After iv administration of 100 micrograms DGAVP, CSF concentrations were detectable for 90 min. Transport from plasma to the central nervous system was linear. The BBB transport clearance value was 1.0 +/- 0.3 microliters/min, and 0.026 +/- 0.007% of the administered dose was transported into the central nervous system. Results demonstrate that, within the concentration range studied, DGAVP is transported across the BBB by passive diffusion, although to a very low extent.