The effect of concomitantly administered antacids on the bioavailability of lornoxicam, a novel highly potent NSAID.

Antacids are used in the treatment of upper gastrointestinal side-effects during therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). Since pharmacokinetic interactions between antacids and NSAIDs have been reported, it was investigated whether aluminium and magnesium hydroxide (Maalox as oral suspension) or aluminium hydroxide and calcium carbonate (Solugastril as oral gel) influenced the bioavailability of Lornoxicam (rINN), a new potent NSAID from the chemical group of the oxicams. Eighteen male volunteers were given 4 mg of Lornoxicam as a film-coated tablet either alone or together with 10 ml of Maalox or 10 g of Solugastril in an open, randomized, three-way cross-over study. The levels of Lornoxicam in plasma were determined by HPLC following solid-phase extraction. It was found that none of the antacids changed significantly any of the following pharmacokinetic parameters: elimination half-life (t1/2 beta), concentration at peak time (Cmax), time to reach the peak (tmax) and area under the curve to infinity (AUCo-infinity). The results indicate that the concomitant administration of antacids did not influence the pharmacokinetic profile of Lornoxicam. Furthermore they confirm the short elimination half-life of Lornoxicam in man, which is markedly shorter than that of other oxicam-type compounds.

Studies on hydroxyethyl starch. Part II: Changes of the molecular weight distribution for hydroxyethyl starch types 450/0.7, 450/0.5, 450/0.3, 300/0.4, 200/0.7, 200/0.5, 200/0.3 and 200/0.1 after infusion in serum and urine of volunteers.

32 volunteers, none of whom showed any symptoms for kidney, liver or pancreas disease, were given by infusion 500 ml of various type of hydroxyethyl starch (HES) at a concentration of 6% (450/0.7, 450/0.5, 450/0.3, 300/0.4) as well as of 10% (200/0.7, 200/0.5, 200/0.3, 200/0.1) over a period of 30 min. After infusion both the Mw and the Mn diminished. The rate of elimination of HES from serum entirely depended on molar substitution and not on Mw. The quotient Mw/Mn decreased considerably over the entire test period. The lower molecular weight limit in serum remained relatively the same at 60,000 Daltons. Maximum molecular weight limit of urine, too, was 60,000 Daltons.

Comparison of chlortenoxicam and indomethacin on frusemide-induced diuresis.

A single oral dose of chlortenoxicam 4 mg, a new non-steroidal anti-inflammatory drug, significantly antagonized the diuretic and natriuretic actions of frusemide when compared with placebo in normal human volunteers. Indomethacin 50 mg significantly reduced the natriuretic, but not diuretic action of frusemide.

Studies on hydroxyethyl starch. Part I: Molecular characterization by size exclusion chromatography coupled with low-angle laser light scattering.

Two commercially available hydroxyethyl starch (HES) preparations (in clinical use as plasma expanders) specified with Mw = 450,000/MS = 0.7 and Mw = 200,000/MS = 0.5, respectively, and three experimental HES-samples (supposingly similar to the commercial product with the specification 450,000/0.7, except of one with MS = 0.5) were studied. The latter were prepared via acid or enzymatic hydrolysis of waxy-maize starch. Each of the samples was characterized by its intrinsic viscosity and molar substitution, and was studied with low-angle laser light scattering (LALLS) and with size exclusion chromatography (SEC) coupled with LALLS. The weight-average molecular weight Mw of the commercial samples was found to be 60-80% higher than the value given in the product declaration. This discrepancy can be explained by the argument that previous measurements were not carried out at sufficiently small scattering angles to enable reliable extrapolation to zero angle. The calibration functions Mw(v) of the individual HES-samples measured by SEC/LALLS-coupling are identical over a broad range of the elution volume v and are used for calibration of conventional SEC in a subsequent paper. The small, but detectable differences in the Mw(v)-functions indicate interesting differences between these HES-preparations with respect to the effective hydrodynamic density of the branched HES-molecules.

Chlortenoxicam pharmacokinetics in young and elderly human volunteers.

The pharmacokinetics of chlortenoxicam, a new non-steroidal anti-inflammatory drug, have been compared in young and elderly healthy human volunteers. Chlortenoxicam was found to have a relatively short mean elimination half-life of about 4 hours, with considerable inter-subject variability, but there was no significant difference between young and elderly subjects. There was no evidence of accumulation with repeated administration. No unchanged chlortenoxicam was found in urine from any subject, suggesting that it undergoes extensive metabolism in man.