Studies on digitalis. 23. Blood‐brain barrier of digitoxin in humans

Abstract

AbstractData on the cerebrospinal fluid concentrations of digitoxin in man have been lacking. Aim of the present study was to investigate serum and cerebrospinal fluid concentrations of digitoxin. Eleven patients with normal cerebrospinal fluid composition, normal serum albumin values, normal renal and hepatic function and normal hematologic tests were given a single dose of 0.6 mg digitoxin. Serum and cerebrospinal fluid were collected 16 h after the dose, and assayed by radio‐immunoassay, serum digitoxin protein binding was measured with equilibrium dialysis.Mean serum digitoxin concentration was 12.4 ng/ml (SD 2.6) and mean CSF concentration 0.84 ng/ml (SD 0.22) giving a CSF/serum ratio of 0.07 (SD 0.03). Serum digitoxin protein binding was 97.4% (SD 0.4) and the calculated CSF/free serum digitoxin ratio was thus 2.94 (SD 1.43).Free serum digitoxin concentrations are more relevant for pharmacologic effect than total serum digitoxin concentrations and also for passage into the central nervous system. Using free drug concentrations the ratio between digitoxin in serum and CSF is lower than reported values for digoxin indicating a higher penetrance of digitoxin into the central nervous system. This corresponds well with the higher lipid solubility of digitoxin. Post mortem studies have shown that concentrations are higher in cerebral tissue than in CSF for digoxin. Determination of CSF concentrations thus probably underestimates the penetrance of digitalis glycosides into the central nervous system, but may serve as a useful indicator of variance among digitalis glycosides.