Transsynovial distribution of ibuprofen in arthritic patients.

Clinical pharmacology and therapeutics (1981-04-01)
J B Whitlam, K F Brown, M J Crooks, G F Room
ABSTRACT

Free and total ibuprofen levels in serum and synovial fluid (SF) were determined in one male and 14 female arthritic patients (mean age 56 yr, range 19 to 77) after 400 mg three times daily for 2 days. Free drug was separated by ultrafiltration and assayed by a new highly sensitive and precise gas chromatographic-mass spectrometric technique. Total protein and albumin were assayed by automatic analyzer, and the routine serum biochemical profile obtained. Serum and SF nonesterified fatty acids (NEFAs) were methylated and assayed by gas chromatography. While both total protein and albumin levels were lower (P less than 0.01) in SF, NEFA levels did not differ (p greater than 0.05). Ibuprofen readily partitions into and binds strongly to joint fluid, the total level being about half that in serum. The ratio of total ibuprofen in SF to that in serum (x = 0.41 +/- 0.17) correlated with the albumin concentration ratio (r = 0.886) indicating that albumin binding is an important determinant of ibuprofen transsynovial distribution. A low total ibuprofen SF/serum ratio, apparent for three patients on concomitant aspirin therapy, is consistent with reports of an ibuprofen-salicylate interaction. Free ibuprofen in SF (0.192 +/- 0.086 microgram ml-1) did not differ (p greater than 0.05) from serum free levels (x = 0.251 +/- 0.139 microgram ml-1), supporting the concept of the synovial cavity as a compartment readily accessible to unbound drug species. Multiple regression analyses revealed relative independence of free concentration on total levels, and the small positive and negative influences of NEFAs and albumin concentrations. Bilirubin, uric acid, cholesterol, triglycerides, and chloride ion did not correlate with serum free concentration.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ibuprofen, ≥98% (GC)
Supelco
Ibuprofen, Pharmaceutical Secondary Standard; Certified Reference Material
Ibuprofen for peak identification, European Pharmacopoeia (EP) Reference Standard
Supelco
Ibuprofen
Ibuprofen, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Ibuprofen, meets USP testing specifications
Supelco
Ibuprofen solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®

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