RESUMO
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.
Assuntos
Antagonistas dos Receptores Histamínicos H1/farmacocinética , Teofilina/análogos & derivados , Adulto , Cromatografia Líquida de Alta Pressão , Antagonistas dos Receptores Histamínicos H1/sangue , Humanos , Masculino , Teofilina/administração & dosagem , Teofilina/sangue , Teofilina/farmacocinéticaRESUMO
A direct high-performance liquid chromatographic enantioseparation on a chiral stationary phase using a protein as chiral selector was achieved for some dihydropyridines with different structural groups (amine, amide, acid and hydroxyl groups). The protein involved was alpha 1-acid glycoprotein and the work was mainly carried out with an EnantioPac column. An improved version of this chiral column (Chiral-AGP) was compared with the previous one and gave interesting results.
Assuntos
Di-Hidropiridinas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Orosomucoide/análise , Estereoisomerismo , TemperaturaRESUMO
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.
