AJP - Regulatory, Integrative and Comparative Physiology, Vol 242, Issue 3 339-R348, Copyright © 1982 by American Physiological Society
Drug entry into and distribution within brain and cerebrospinal fluid: [14C]urea pharmacokinetics
S. I. Rapoport, R. Fitzhugh, K. D. Pettigrew, U. Sundaram and K. Ohno
A four-compartment model was derived to analyze drug exchange among
cerebral capillary plasma, cerebrospinal fluid (CSF), and the brain
extracellular and intracellular (or bound) compartments. Equations that
were derived incorporated the factor of cerebral blood flow. They were fit
by nonlinear least squares to measured brain, plasma, and CSF (when
available) concentrations of [14C]urea in the rat, in response to a step
increase in plasma concentration, to intravenous infusion, or to a bolus
injection of tracer. Best-fit values for the transfer constants were
consistent among the three administrative regimens and agreed with
published values, when available. Expressions also were derived and
numerically evaluated for the lower limit of the brain extracellular space,
for half times of brain [14C]urea uptake, and for the steady-state
brain/plasma distribution volume. The model should make it possible to use
transfer constants obtained for a given drug from one study (e.g., constant
plasma concentration) to predict brain concentrations from measured plasma
concentrations in other acute or chronic studies.
