The pharmacokinetics of vigabatrin in rat blood and cerebrospinal fluid.
OBJECTIVE
Data on the blood pharmacokinetics of vigabatrin, an antiepileptic drug with a unique and novel mechanism of action, in the rat are sparse. Additionally, little is known of the kinetics of vigabatrin in the central cerebrospinal fluid (CSF) compartment. We therefore investigated the rate of penetration into and the inter-relationship between serum and CSF compartments following systemic administration of vigabatrin in the rat.


METHODS
Sprague-Dawley rats were implanted with a jugular vein catheter and a cisterna magna catheter for blood and CSF sampling, respectively. Vigabatrin was administered by intraperitonial injection at three different doses (250, 500 and 1000mg/kg) and blood and CSF collected at timed intervals up to 8h. Vigabatrin concentrations in sera and CSF were determined by high performance liquid chromatography.


RESULTS
Vigabatrin concentrations in blood and CSF rose linearly and dose-dependently and the time to maximum concentration (Tmax) was 0.4 and 1.0h, respectively. Vigabatrin is not protein bound in serum and its elimination from serum (mean t1/2 values, 1.1-1.4 h) is rapid and dose-independent. The efflux of vigabatrin from CSF was significantly slower than that seen for serum (mean t1/2 values, 2.2-3.3h).


CONCLUSIONS
The kinetics of vigabatrin are linear with rapid entry into CSF. However, although vigabatrin CSF kinetics parallel that seen in serum, CSF vigabatrin concentrations represent only 2% of concentrations seen in serum and do not reflect free drug concentrations in serum.
Tong
X
X
Department of Clinical and Experimental Epilepsy, Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
Ratnaraj
N
N
Patsalos
P N
PN
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020888:Vigabatrin / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D020888:Vigabatrin