The concentration-time profiles of rifampicin and pyrazinamide in the cerebrospinal fluid (CSF) and plasma of the rabbit (New Zealand white rabbits of both sex, 4.0-5.5 kg) were studied after oral administration. CSF samples and simultaneous blood 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 (0.2 ml) were obtained from the cisterna magna. Using this rabbit model, 8 CSF and 20 blood samples can be obtained from the rabbit in a 24 h period after drug administration. In 6 rabbits the mean CSF-plasma ratios for pyrazinamide at 0.5, 1, 4, 6 and 24 h was 1.23, 1.13. 1.05. 1.19 and 0.75, respectively, while in 4 rabbits after oral rifampicin dose, the ratios were 0.52, 0.76, 1.17, 0.89 and 0.78 at 0.5, 1, 4, 6 and 12 h, respectively. The results indicate that the small pyrazinamide molecule with good lipid solubility penetrates readily into the CNS while rifampicin traverses the blood brain barrier with difficulty due perhaps to its bulky molecule and low water solubility.
- Rabbit model,
- Concentration-time profile in CSF and plasma,
- CSF-plasma concentration ratio
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