The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accommodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).
Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations. Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24 h post-dose. Results Maximum plasma concentrations (C max ) of both the (R)-and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50-80%. The area under concentration-time data (AUC) was unaffected, and, hence, C max /AUC was increased by buffering. Time to C max (t max ) and mean residence time (MRT) tended to be or was shortened by buffering. Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.
Voglibose did not interact with glibenclamide on a pharmacokinetic level. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
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