Effect of perfusate pH on reduction of quinidine capillary permeability by albumin in isolated perfused rat heart.
It has been suggested that albumin reduces quinidine capillary permeability (PS) in the single-pass perfused heart preparation by reducing paracellular transport of quinidine ions. Using this preparation, we examined the effect of albumin (0.1 per cent) on quinidine PS at perfusate pH's of 7.1 and 7.9 during uptake of quinidine (19 microM) and also during washout of the drug using a randomized design. Quinidine PS was approximately 16 ml/min/g heart at pH 7.9 and was not altered by the presence of albumin in perfusate. At pH 7.1, in the absence of albumin, quinidine PS was also 16 ml/min/g, but in the presence of albumin (0.1 per cent) PS was reduced significantly to approximately 5 ml/min/g (P < 0.001). In the absence of albumin PS was the same at pH 7.1 and 7.9 in spite of a greater degree of ionisation of quinidine at pH 7.1. This suggests that there is significant uptake of ionised quinidine at pH 7.1. The greater effect of albumin on PS at pH 7.1 supports the hypothesis that albumin reduces paracellular transport of quinidine ions.
Morgan
D J
DJ
Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, Melbourne, Australia.
Xu
C L
CL
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011485:Protein Binding; D011802:Quinidine / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*
D012709:Serum Albumin; D011802:Quinidine