Pharmacokinetics of GM1 ganglioside following parenteral administration

The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each dose was administered to separate groups of 12 volunteers. GM1 levels were determined in plasma, urine, and faeces by a method based on the property of the cholera toxin beta subunit to react specifically with GM1 ganglioside. A non-compartmental model was applied to determine standard pharmacokinetic parameters. The average AUC increased with dose (1002 +/- 121.2, 1306 +/- 146.1, 3155 +/- 121.6 micrograms mL-1 h after 100, 200, 300 mg, respectively). Plasma clearance was less than 3 mL min-1 and the distribution volume was close to the plasma volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for all doses. GM1 was not detected in urine, while in faeces the amount of GM1 determined was similar to the baseline values obtained before dosing.     

A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma

Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total number of reported skin metastasis of vaginal carcinoma is only one. We present another case with an unusual manifestation of vagina carcinoma metastasis: skin metastasis presenting as a leg ulcer on the lower leg.     

Pharmacokinetics of isosorbide mononitrate in a new sustained release oral form in comparison with a conventional formulation

40 mg of isosorbide mononitrate (isosorbide-5-mononitrate, IS5MN) in conventional (Ismo 20) and sustained release formulations (Ismo Diffutab) were administered to 5 male healthy volunteers. The administration of the sustained release formulation was repeated for seven days in order to evaluate the possible occurrence of accumulation. Pharmacokinetic data showed that the sustained release formulation reached significantly lower and delayed mean peak plasma levels compared with the conventional formulation, respectively 452.8 +/- 67.8 ng/ml and 706.7 +/- 57.3 (mean +/- SE) (p less than 0.05). Peak times were 4.6 +/- 0.2 and 2.4 +/- 0.2 (p less than 0.005) h, respectively. A longer plasma half-life together with larger AUC for the sustained release formulation was also observed. The pharmacokinetic parameters of the sustained release formulation are consistent with a therapeutic usefulness and suggest further clinical evaluation.