[The effect of orthostasis on the fructosamine value]. / Einfluss der Orthostase auf den Fructosamin-Wert.

With the introduction of an improved method for the determination of fructosamine a new tool is available for the monitoring of diabetes. This method provides a good reproducibility together with a standardized quality control and is easily applicated to automated clinical chemistry analyzers. Besides the analytical performance in general the impact of preanalysis on fructosamine values is important for routine work. In a study with 20 volunteers the impact of orthostasis has been investigated. Changes in fructosamine concentration correspond to a shift in the concentration of other analytical parameters related to serum proteins.

Pharmacokinetics of picumast dihydrochloride and its active metabolites M1 and M2 in humans.

The pharmacokinetics of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and the pharmacodynamically active metabolites M1 and M2 as well as the absolute bioavailability of picumast dihydrochloride have been studied in healthy volunteers after oral administration of the drug in doses which were considerably higher than therapeutically used. After intravenous administration of 10 mg picumast dihydrochloride a peak concentration of 182 ng/ml was achieved at the end of the 1 h infusion. Picumast dihydrochloride was extensively distributed to the tissues (Vz = 130 l) and almost exclusively eliminated by hepatic metabolism (total clearance 95 ml/min, amount of unchanged compound excreted in urine below detection limit). Median elimination half-life was 16.5 h. The absolute bioavailability reached 57%. The relative bioavailability of picumast dihydrochloride was 20% higher after a meal. After a 20 mg oral dose maximum concentrations between 129 and 284 ng/ml were achieved within 1.3 h. The elimination half-life ranged from 10-26 h. No difference existed between oral (14.5 h) and intravenous administration. The metabolites M1 and M2 in human plasma peaked at 3.4 and 4 h. With 41 h (M1) and 34 h (M2) they exhibited longer half-lives than the parent compound. So under steady state conditions the average plasma concentration of these metabolites amounted to about 68% and 40%, resp., of the unchanged drug as calculated by the ratio of the total areas. The total amount of metabolites M1 and M2 recovered in urine was 6.88% of the oral dose administered, i.e. 6.8% M1 and 0.08% M2. The renal clearance was determined as 28 and 0.5 ml/min for M1 and M2, resp.

Study of potential kinetic interactions of picumast dihydrochloride and theophylline in vitro and after oral administration in man.

The kinetic interaction of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin dihydrochloride) and theophylline has been studied in vitro (displacement from protein binding) and in vivo in healthy male non-smokers after oral administration. In a randomized, three-way cross-over study, 12 subjects received at weekly intervals either separated or combined single doses of picumast dihydrochloride (10 mg) and theophylline (7 mg/kg b.w.) Picumast and its metabolites were analysed in plasma and urine up to 24 h and theophylline was assayed in plasma during the same time. Theophylline pharmacokinetic parameters like time to peak concentration, peak concentration, elimination half-life, area under the plasma concentration-time curve and oral clearance were not changed after a concomitant dose of picumast dihydrochloride. The combination of theophylline and picumast dihydrochloride revealed no significant changes in the picumast pharmacokinetic parameters t1/2, tmax and CLR. However, Cmax and AUC0-24 decreased significantly by 11% and 7%, resp. Additional theophylline administration significantly increased peak concentration of the intermediate active metabolite M2 by 23% from 7 to 8.6 ng/ml. The absorptive parameters, i.e. time to peak and peak concentration of M1 as well as the AUC calculated from 0-24 h and the renal clearance did not differ in single or combined picumast dihydrochloride administration. A supplementary in vitro study showed no change in plasma protein binding of picumast (100 ng/ml) in the presence of theophylline (20 micrograms/ml) and vice versa. In all volunteers picumast dihydrochloride proved to be safe and well tolerated and treatment was not negatively influenced by theophylline co-administration.(ABSTRACT TRUNCATED AT 250 WORDS)