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Present study revealed that metronidazole penetrates well into gingival crevice fluid and saliva. Metronidazole concentrations in crevice fluid are about equal to the protein unbound drug concentrations in plasma. Therefore, general pharmacokinetic data of metronidazole can be also applied in the treatment of periodontal disease and in the design of respective treatment regimens.

P-glycoprotein (Pgp) is a member of the ABC-transporter family, and in humans, is encoded by the MDR1 gene. Recently, several single-nucleotide polymorphisms in the MDR1 gene were identified. The aim of the present study was to evaluate the effect of the MDR1 genetic polymorphisms G2677T and C3435T on Pgp activity in CD56+ and CD4+ peripheral blood cells. Using flow cytometry, rhodamine 123 (Rh123) efflux was determined in 46 male healthy volunteers. Median Rh123 fluorescence in control sample, after baseline dye uptake, was set as 100%. Rh123 fluorescence in efflux samples, exposed to different efflux periods, was used to calculate the percentage of Rh123 retained in the cells in comparison with control. There was no significant difference in Rh123 efflux in CD56+ cells after 5, 10, 15, and 30 min efflux between individuals with different MDR1 genotypes. Also, in CD4+ cells after 15, 30, 60, and 90 min, Rh123 efflux did not reveal statistically different results for the three genotypes at 2677 and 3435. Rh123 efflux was not enhanced by a 10-day rifampin administration, as determined in 15 individuals before and after rifampin treatment. In conclusion, we found no impact of the MDR1 G2677T and C3435T polymorphisms on Pgp activity in CD56+ and CD4+ peripheral blood lymphocytes.

DSP-4 is a neurotoxin highly selective for the noradrenergic nerve terminals originating from the locus coeruleus. Preliminary data suggested that its effect in a typical screening test for antidepressant drugs, the forced swimming test, is biphasic dependent on the dose. In the present study, DSP-4 was administered in four doses (5, 10, 30 and 50mg/kg) to male Wistar rats. Administration of the neurotoxin had a dose-dependent biphasic effect on immobility time in the forced swimming test 8 and 9 days later. Thus, DSP-4 at the dose of 10mg/kg increased immobility, but higher doses reduced this measure. The reduction of noradrenaline concentration in the frontal cortex and hippocampus was dose-dependent starting from the dose 10mg/kg. Cortical beta-adrenoceptor binding was increased by DSP-4 treatment at the doses 30mg/kg and 50mg/kg. These results suggest that the increase in immobility time in the forced swimming test is associated with presynaptic changes in noradrenaline availability, whereas the decrease in immobility observed after more complete denervation is associated with postsynaptic receptor supersensitivity.