Effect of serum from renal failure and cirrhotic patients on the blood-brain barrier permeability to DL-propranolol in rats.
Our previous studies using an in vivo tissue-sampling single-carotid injection method have shown that the transport of DL-propranolol into rat brain is inhibited by the serum from rats with uranyl nitrate-induced acute renal failure. The present studies were designed to examine the effect of serum from patients with renal or liver disease on the transport of DL-propranolol into the rat brain. While the binding of DL-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 (ET), the blood-brain barrier permeability surface area product (PSapp), and PSapp corrected for the unbound fraction (PSuapp) 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, ET, 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 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) representing the degree of renal failure and the transport parameters (ET, PSapp, or PSuapp) of DL-propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000818:Animals; D001812:Blood-Brain Barrier; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011433:Propranolol / Q000493:pharmacokinetics*; D051381:Rats
D011433:Propranolol