Penetration into and elimination from the cerebrospinal fluid of diltiazem, a calcium antagonist, in anesthetized rabbits.

Penetration into and elimination from the cerebrospinal fluid (CSF) of diltiazem were studied following intravenous (i.v.) or intra-cisternal (i.c.) administration of 14C-diltiazem to anesthetized rabbits. 14C-Diltiazem rapidly penetrated into the CSF through the blood-CSF barrier after i.v. injection (1 mg/kg). A CSF level of the radioactivity attained the peak (0.13 microgram eq./ml) 5 min after i.v. injection and declined bi-exponentially with rapid initial half-life of 3.8 min (5-15 min) and second half-life of 2.7 h (15 min-8 h). A CSF/plasma ratio was 0.05-0.2 throughout the observation period. After i.c. administration (100 micrograms/body), the CSF level of the radioactivity decreased with a half-life of 7.5 min up to 1 h. The CSF level was maintained above 10(-7) mol/l until 2-3 h. Elimination half-life of 14C-diltiazem after i.c. injection was much more similar to that of 3H2O than 14C-inulin, indicating that the main elimination route of this compound from the CSF is diffusion into the brain, followed by rapid diffusion into the cerebral capillary, rather than filtration from the sub-arachnoid villi. An autoradiographic investigation supported the above route of elimination.