Kinetic Analysis of the CNS Disposition of Drugs in the Renal and Hepatic Failure

present studies designed to examine The effect of serum from patients with renal or liverdisease on the transport of propranolol into the rat brain. While the binding of propranolol toserum from cirrhotic patients was significantly decreased compared to normal serumthere no change for the serum from patients with renal failure. In the carotid injectionstudies, the brain transport parameters such as the brain uptake index （BUI）the unidirectional extraction ratio (E)the blood - brain barrier permeability surface area product （PSapp）and PSapp corrected for the unbound fraction （PSu）in rats injected with serum from patients with renal failure were significantly减轻toapproximately 40-53% of those in controls. No change in BUI， E，PSapp was found in rats injected with serum from cirrhotic patients. However，the cirrhotic patients adopted in the present study had relatively mild liver disease（判断）the biochemical blood test, and we cannot refer…More to the More severe cirrhotic patients only from this study. Moreover，重要的correlations were observed between the biochemical parameters （blood urea nitrogen）serum creatinine concentration repesenting the degree of renal failure and the transport parametersPSapp或PSu，app) of propranolol. As previously studied with the experimental acute renal failure rats，这些结果indicate the decrease in the transport of propranolol into rat brain may also dueto the presence of an inhibitory factor in the serum from renal failure patients.To elucidatethe characteristics of promotion factor (s) in rat serum required for the protein-mediated transportof drugs into the brain，我们examined the brain uptake of propranolol as a model drug using the体内BUI method in rats.The protein - mediated transport was not observed in rats injected with The buffer solution containingeither various concentrations of purified rat alpha1-acid glycoprotein (alpha1-AGP) or rat albumin。When the filtrate from rat serum used as an injection vehicle to which a physiologicalconcentration of purified rat serum proteins added，protein mediated transport of propranolol被监测在rat brain. Moreover，the ability of protein-mediated transport of propranolol was reduced in rats injected with thedialyzed serum compared with the undialyzed serum.这些results suggest that the dialyzablepromotion factor in serum is required for the protein—mediated transport of propranolol into thebrain . less

The present studies were designed to examine the effect of serum from patients with renal or liver disease on the transport of propranolol into the rat brain. While the binding of propranolol to serum from cirrhotic patients was significantly decreased compared to normal serum, there was no change for the serum from patients with renal failure. In the carotid injection studies, the brain transport parameters such as the brain uptake index (BUI), the unidirectional extraction ratio (E), the bloodーbrain barrier permeability surface area product (PSapp), and PSapp corrected for the unbound fraction (PSu, app) in rats injected with serum from patients with renal failure were significantly reduced to approximately 40-53% of those in controls. No change in BUI, E, and PSapp was found in rats injected with serum from cirrhotic patients. However, the cirrhotic patients adopted in the present study had relatively mild liver disease (judging from the biochemical blood test), and we cannot refer … More to the more severe cirrhotic patients only from this study. Moreover, significant correlations were observed between the biochemical parameters (blood urea nitrogen, serum creatinine concentration) repesenting the degree of renal failure and the transport parameters (E, PSapp or PSu, app) of propranolol. As previously studied with the experimental acute renal failure rats, these results indicate that the decrease in the transport of propranolol into rat brain may also due to the presence of an inhibitory factor (s) in the serum from renal failure patients.To elucidate the characteristics of promotion factor (s) in rat serum required for the protein-mediated transport of drugs into the brain, we examined the brain uptake of propranolol as a model drug using the in vivo BUI method in rats. The proteinーmediated transport was not observed in rats injected with the buffer solution containing either various concentrations of purified rat alpha1-acid glycoprotein (alpha1-AGP) or rat albumin. When the filtrate from rat serum was used as an injection vehicle to which a physiological concentration of purified rat serum proteins was added, the protein mediated transport of propranolol was observed in the rat brain. Moreover, the ability of protein-mediated transport of propranolol was reduced in rats injected with the dialyzed serum compared with the undialyzed serum. These results suggest that the dialyzable promotion factor in serum is required for the proteinーmediated transport of propranolol into the brain. Less