Disposition of ethmozine in cerebrospinal fluid and plasma of rabbits
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The concentration — time profiles of ethmozine, a newly introduced anti-arrhythmic drug, in the cerebrospinal fluid (CSF) and plasma of six rabbits (New Zealand white rabbits of both sexes, 4.0–5.0 Kg) were studied after intravenous bolus administration. CSF samples at various intervals were obtained while the animal was lightly anaesthetized with intravenous thiopentone (40 mg Kg−1 ) and blood samples at other intervals were taken while the animal was conscious. Blood samples (1 ml) were collected from the implanted cannula of the ear artery while CSF samples (0.3 ml) were obtained from the cisterna magna. The plasma concentrations of ethmozine in six rabbits declined rapidly after intravenous injection for up to 30 min. then slowly over 12 h. Using non-compartmental analysis, the mean ( ± S.E.M.) elimination half-life, mean residence time, plasma clearance and volume of distribution at steady state were 13.9±9.2h, 19.9±13.4 h, 2.3 Lh−1 and 26.8±7.9 L respectively. The mean CSF-plasma concentration ratios for ethmozine at 0,5, 1.0, 2.0, 4.0, 8.0 and 12.0 h were 0.17, 0.14, 0.16, 0.16, 0.23 and 0.22 respectively. The results suggest that ethmozine is able to penetrate into the CSF from the general circulation and this may be related to its adverse effects on the central nervous system.
Key wordsEthmozine concentration — time in CSF and plasma CSF-plasma concentration ratio
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