Arzneimittel Forsch
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Arzneimittel Forsch · Jan 2000
Randomized Controlled Trial Clinical TrialPharmacokinetics of diclofenac after oral administration of its potassium salt in sachet and tablet formulations.
This paper reports the results of a pharmacokinetic study involving 24 healthy volunteers and designed to characterise the rate and extent of diclofenac absorption after the administration of a single dose of diclofenac (CAS 15307-86-5) potassium salt 50 mg in sachet (Voltfast) and tablet (Cataflam) formulations. Timed plasma concentrations of diclofenac during a 12-h-period after dosing were measured by means of HPLC with UV detection at 275 nm and a quantification limit of 10 ng/ml; the method was fully validated for pharmacokinetic purposes. These plasma concentrations were used to calculate Cmax, tmax, trapezoidal AUC0-t and AUC0-infinity and t1/2 by means of noncompartmental analysis. ⋯ The average time to peak concentration with the tablets was 53.10 min. The extent of absorption of the sachets and tablets was similar, with AUC0-infinity values of respectively 1362 and 1214 ng.ml-1.h, and a 90% confidence interval 1.05-1.20. The highly soluble potassium salt of diclofenac was rapidly absorbed, especially in its sachet formulation, and thus appears to be an invaluable analgesic agent that is particularly useful for quick pain relief.
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Arzneimittel Forsch · Jan 2000
Behavioural effects of fluoxetine and tianeptine, two antidepressants with opposite action mechanisms, in rats.
The behavioural effects of two antidepressants with opposite molecular mechanisms, tianeptine 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin - 11-yl)amino]heptanoic acid S,S-dioxide, CAS 66981-73-5) 5 mg/kg p.o., a serotonin reuptake enhancer, and fluoxetine (+/-)-N-methyl-3-phenyl-3-[(alpha, alpha, alpha-trifluoro-p- tolyl)oxy]propylamine, CAS 54910-89-3) 5 mg/kg p.o., a serotonin reuptake inhibitor, were compared after single and prolonged administration (7 and 14 days) once daily). In all experiments the drug effects were noted at the peak activity time: 30 min after tianeptine and 60 min after fluoxetine administration. In the immobility time test both drugs had a shortening effect on immobility time only after prolonged administration or, in single treatment, after joint administration. ⋯ In the test for sedative action (in the Activity Meter AM-1, where the movements of the animals are counted electronically) only after prolonged treatment with tianeptine a diminished locomotor activity could be observed. It is concluded that in the action of the drugs (beside the effect on serotonin uptake) other mechanisms must play an important role. The diminished locomotor activity after tianeptine suggests an influence on the dopaminergic or GABA-Receptor system.