Protein binding of salicylate in cutaneous hepatic porphyria |
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Authors: | Wilson H. Steele Susan Wallace Boobis Michael R. Moore Abraham Goldberg Martin J. Brodie David J. Sumner |
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Affiliation: | (1) Department of Materia Medica and Therapeutics, University of Glasgow, UK;(2) Present address: Department of Clin. Pharmacol, Royal Postgrad. Med. School, Hammersmith Hospital, London;(3) Department of Clinical Physics and Bioengineering, Stobhill General Hospital, G21 3UW Glasgow, Scotland |
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Abstract: | Summary (1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltration. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction. |
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Keywords: | Protein binding cutaneous hepatic porphyria ultrafiltration salicylates |
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