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1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration‐time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l‐1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/‐ 0.15 h‐1 with a lag time (tlag) of 0.24 +/‐ 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/‐ 12 h) and appreciable drug concentrations were still measurable (27 mg l‐1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady‐state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.

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The multiple-dose pharmacokinetics of the new H1-receptor antagonist, tazifylline, were investigated in healthy volunteers. From single-dose data, tazifylline appeared to be rapidly absorbed (median tmax of 0.6 h) and eliminated (t1/2 = 1.0 +/- 0.2 h). However, plasma levels measured on days 3 and 8 of the multiple-dose regimen (10 mg b.i.d. for 8 days) indicated moderate accumulation. A two-compartment model best described multiple-dose data with a terminal half-life of 15.6 +/- 7.6 h consistent with twice-daily dosing of tazifylline.