Effect of age on distribution of zidovudine (azidothymidine) into the cerebrospinal fluid of Macaca nemestrina.

The brain tissue is an important target for anti-HIV drug therapy. Since the permeability of the blood-brain and blood-cerebrospinal fluid (CSF) barriers may differ between neonates and adults, we have determined the effect of age on the distribution of zidovudine (ZDV or azidothymidine) into the CSF in the macaque (M. nemestrina). Five newborn macaques were administered ZDV (iv bolus, 5 mg/kg) at various ages (2 days to 4 months). Both CSF (cisternal) and venous blood samples were obtained at approximately 60 and 90 min after drug administration. In another series of experiments, adult female macaques received ZDV as either an iv bolus (5 and 10 mg/kg) or an infusion for at least 12 hr. CSF (lumbar) and venous blood samples were obtained at approximately 60 and 90 min after iv bolus and at more than 12 hr after iv infusion. ZDV concentration in the CSF and the plasma samples was determined by high-performance liquid chromatography. The CSF/plasma concentration ratio of ZDV in the newborn and adult macaques, after iv bolus administration, was independent of time. In addition, no significant (P > 0.05) difference was observed in the pooled iv bolus ZDV CSF/plasma concentration ratio between the adult group (0.236 +/- 0.058) and the newborns (0.213 +/- 0.039). Moreover, the ZDV CSF/plasma concentration ratio in the adults and the newborns, after iv bolus administration, was found not to be significantly (P > 0.05) different from the ratio obtained at steady state in the adults (0.224 +/- 0.094). These data indicate that the distribution of ZDV into the CSF in macaque neonates and adults is similar.