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Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation.
Author(s) -
Ouweland FA,
Franssen MJ,
Putte LB,
Tan Y,
Ginneken CA,
Gribnau FW
Publication year - 1987
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1987.tb03028.x
Subject(s) - naproxen , rheumatoid arthritis , pharmacokinetics , medicine , bioavailability , concomitant , volume of distribution , arthritis , albumin , pharmacology , area under the curve , serum albumin , gastroenterology , pathology , alternative medicine
Patients with rheumatoid arthritis often have hypoalbuminaemia as a sign of disease activity. In view of the extensive binding of naproxen to albumin, the pharmacokinetics of total and unbound drug were studied in eight patients and eight healthy male volunteers during chronic intake of 500 mg twice daily. The area under the serum concentration‐ time curve of total naproxen during a dose interval, AUC (0,12), smaller in patients (641 +/‐ 101 mg l‐1 h) than in volunteers (896 +/‐ 85 mg l‐1 h; P less than 0.0001). The unbound naproxen AUCu (0,12) was larger in patients (1.9 +/‐ 0.9 mg l‐1 h) than in volunteers (0.7 +/‐ 0.2 mg l‐1 h; P less than 0.01). The higher unbound naproxen concentrations in patients were accompanied by an approximately 40% increase in apparent clearance/bioavailability (CL/F) and a 60% increase in volume of distribution (V/F). Both CL/F and V/F were inversely correlated with the individual serum albumin concentration (r = 0.76, P less than 0.001; r = −0.85, P less than 0.001, respectively). The high unbound naproxen concentration in the serum of patients with active rheumatoid arthritis and concomitant hypoalbuminaemia is not known to be accompanied by an increase in side effects and may be beneficial if anti‐inflammatory effects correlate with unbound drug concentration.