TY - JOUR
T1 - Decreased protein binding of salicylates in Kawasaki disease
AU - Koren, Gideon
AU - Silverman, Earl
AU - Sundel, Robert
AU - Edney, Peter
AU - Newburger, Jane W.
AU - Klein, Julia
AU - Robieux, Isabelle
AU - Laxer, Ronnald
AU - Giesbrecht, Ester
AU - Burns, Jane C.
N1 - Funding Information:
Salicylates combined with high intravenous doses of 3,-globulin are the mainstay of therapy in Kawasaki disease.1 The exact clinical effect of salicylates in these patients and the choice of dose have remained controversial; no prospective, controlled trial has adequately addressed these issues. 2 We have demonstrated that malabsorption of salicylates, coupled with their enhanced plasma clearance during the acute phase of KD, accounts for the observed low serum concentration of the drug. 34 These data have been used to justify administration of large doses of salicylate (as Supported in part by U.S. Public Health Service grants HL-01855 and HL-34545. Submitted for publication July 16, 1990; accepted Oct. 3, 1990. Reprint requests: Gideon Koren, MD, Division of Clinical Pharmacology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. *Career Scientist of Ontario Ministry of Health. **Associate of the Arthritis Society. 9/25/25871 high as 180 mg/kg per day) to achieve serum levels of total salicylate of 10 to 25 #g/dl (0.75 to 1.5 mmol/L). 4 In a previous study, we demonstrated reduced protein binding of salicylates in KD patients and speculated that the decreased serum albumin observed in these patients might be responsible) The free (unbound) drug is responsible for the pharmacologic effects of salicylates; hence a decrease in
PY - 1991/3
Y1 - 1991/3
N2 - Because patients with Kawasaki disease have low serum concentrations of salicylates despite high doses, and because the free (unbound) drug is responsible for the pharmacologic effects of salicylates, we assessed salicylate protein binding in patients with Kawasaki disease. During the acute phase of the disease, protein binding of salicylate in 36 children with Kawasaki disease was 73±12%, significantly lower than during the subacute phase (90.4±8.7%; p<0.0005). Mean serum albumin concentration was 29.2±6.4 gm/L during the acute phase and 36.7±7.8 gm/L during the subsequent subacute phase (p<0.005). Salicylate protein binding was affected independently by both serum albumin and total salicylate levels. During the acute phase of Kawasaki disease, children had an average twofold increase in free salicylate compared with normoalbuminemic control subjects. A nomogram has been devised to derive free salicylate levels from the known total salicylate and serum albumin concentrations.
AB - Because patients with Kawasaki disease have low serum concentrations of salicylates despite high doses, and because the free (unbound) drug is responsible for the pharmacologic effects of salicylates, we assessed salicylate protein binding in patients with Kawasaki disease. During the acute phase of the disease, protein binding of salicylate in 36 children with Kawasaki disease was 73±12%, significantly lower than during the subacute phase (90.4±8.7%; p<0.0005). Mean serum albumin concentration was 29.2±6.4 gm/L during the acute phase and 36.7±7.8 gm/L during the subsequent subacute phase (p<0.005). Salicylate protein binding was affected independently by both serum albumin and total salicylate levels. During the acute phase of Kawasaki disease, children had an average twofold increase in free salicylate compared with normoalbuminemic control subjects. A nomogram has been devised to derive free salicylate levels from the known total salicylate and serum albumin concentrations.
UR - https://www.scopus.com/pages/publications/0026059855
U2 - 10.1016/S0022-3476(05)82168-7
DO - 10.1016/S0022-3476(05)82168-7
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C2 - 1999792
AN - SCOPUS:0026059855
SN - 0022-3476
VL - 118
SP - 456
EP - 459
JO - Journal of Pediatrics
JF - Journal of Pediatrics
IS - 3
ER -