Naproxen pharmacokinetics in patients with rheumatoid arthritis during active polyarticular inflammation.

Abstract

1 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. 2 The area under the serum concentration-time curve of total naproxen during a dose interval, AUC (0,12), was smaller in patients (641 ± 101 mg 1-1 h) than in volunteers (896 + 85 mg 1-1 h; P < 0.0001). The unbound naproxen AUCu (0,12) was larger in patients (1.9 ± 0.9 mg 1-1 h) than in volunteers (0.7 ± 0.2 mg 1-1 h; P < 0.01). 3 The higher unbound naproxen concentrations in patients were accompanied by an approxmately 40% increase in apparent clearance/bioavailability (CL/F) and a 60% increase in volume of distribution (VIF). 4 Both CL/F and VIF were inversely correlated with the individual serum albumin concentration (r = 0.76, P < 0.001; r = -0.85, P < 0.001, respectively). 5 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.

Priming innate immune responses to infection by cyclooxygenase inhibition kills antibiotic-susceptible and -resistant bacteria

“…After 1h numbers of surviving bacteria were incubated on Todd Hewitt agar for enumeration 24h later. NS398 and indomethacin were used at concentrations concordant with their IC 80 and at levels x10 higher17, while naproxen was used at a concentration equivalent to serum levels of healthy volunteers after ingestion of 500mg twice daily 18 and a dose x10 lower. Penicillin was used as a reference at 0.075μg/ml bringing about greater than 99% killing of bacteria.…”

Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity

“…This phenomenon is a cascade of biochemical events and is related to the release of pro‐inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferons (IFN) as well as nitric oxide . Inflammatory conditions are associated with pathophysiological changes such as hypoalbuminemia , α 1 ‐acid glycoprotein elevation and a reduction of hepatic drug metabolism . Inflammation increases the binding of basic drugs to α 1 acid glycoprotein , downregulates the majority of liver cytochrome P‐450 enzymes and reduces hepatic blood flow.…”