Bioequivalence of inhaled formoterol fumarate assessed from pharmacodynamic, safety and urinary pharmacokinetic data.

This paper deals with a crossover trial on healthy volunteers performed to obtain combined pharmacodynamic, safety and pharmacokinetic data in order to assess the bioequivalence of formoterol fumarate (CAS 43229-80-7) delivered by mono-dose dry powder inhalers, as test and reference. The trial was carried out on 24 Caucasian healthy male and female volunteers treated with 12 micrograms formoterol fumarate bihydrate capsules for inhalation route. Pharmacodynamics was evaluated through a challenge test with methacholine on the forced expiratory volume in 1 s (FEV1). Safety was achieved from glucose and potassium serum levels assayed on timed samples over a 12-h period cost-dosing and from blood pressure, heart rate and ECG recording. Pharmacokinetics was obtained from urinary excretion of formoterol, assessed by a highly sensitive analytical method (LC-MS-MS). Pharmacodynamic, safety and pharmacokinetic results evidenced the bioequivalence of the two formulations investigated. This investigation is an interesting approach how to assess bioequivalence when the classical approach based on the similarity of plasma concentrations can not be applied.

[Effectiveness of mesoglycan therapy in patients with ischemia of the lower limbs. Preliminary results of a new therapeutic protocol]. / Efficacia del trattamento con mesoglicano in pazienti con ischemia relativa degli arti inferiori. Risultati preliminari di un nuovo protocollo terapeutico.

BACKGROUND: Mesoglycan is a natural glycosaminoglycans preparation, with antithrombotic and pro-fibrinolytic activities, which has been shown to be clinically effective in a number of vascular atherosclerotic disorders with thrombotic risk. METHODS: In the present investigation we studied the effect of mesoglycan in patients with acute episodes of relative lower limb ischemia (Stage IIb according to Leriche-Fontaine classification) coming to our observation. Mesoglycan was administered according to the following schedule: a 10-days period of endovenous mesoglycan (90 mg/day), given in day-hospital regimen, followed by a 20-days period of oral mesoglycan (100 mg/day). The treatment schedule was repeated for two months and then patient continued with oral mesoglycan. We present the preliminary results obtained on 36 patients which were followed for a mean period of 12 months. RESULTS: From February 1995 thirty-six patients, 24 males and 12 females, aged between 45 and 83 years (mean +/- SD: 69.8 +/- 7.5) coming to our observation for acute relative lower limb ischemia were enrolled. At baseline, the diagnosis was Fontaine's IIb stage (walking distance < or = 200 m) in all patients, 17 patients presenting walking distance < 100 m. After 3 and 6 months of mesoglycan treatment a significant improvement of symptoms and signs was observed in all patients but one. At the end of the 6-months period, 29 patients (81% of the study population) became to a Fontaine's IIa degree, with a significant increase in walking distance (in 70% three times their basal value) and improvement of symptoms and recovery time. After treatment, Winsor Index was not significantly modified. Similar results were obtained after 12 months of follow-up. During the study period only one patient included in the trial needed surgical revascularisation. The administration of mesoglycan was well tolerated, with only minor complaints in two patients (one case of headache and one of diarrhea). During the endovenous administration of mesoglycan most patients (81%) presented values of aPTT almost double than baseline, which returned to normal values at the end of the administration. CONCLUSIONS: The present preliminary results show that, in patients with acute episodes of relative lower limb ischemia, mesoglycan (administered according to the described protocol) is an effective and safe agent able to improve symptoms (walking distance, pain, leg appearance) and to possibly delay the need of surgical interventions.

A new device for prevention of postoperative haematoma in the surgery of varicose veins.

The objective of this article is the presentation of a new device, simple, easy to use, at low cost, for the prevention of postoperative haematoma following surgery of varicose veins of the lower limbs. It consists in a two-part device that functions as an elastic and pneumatic bandage, that wraps thigh and leg, with the knee articulation free and that is placed immediately before the stripping of the saphenous vein when all the surgical wounds are closed, except the supramalleolar one. While the head of the stripper is pulled, the device is inflated by air with a compression of 40-50 mmHg and the last surgical wound is sutured. Pneumatic compression is held for 24-36 hours, allowing the patients to walk and, in the meantime, to control the colour and the temperature of the foot. The advantages of this device are: easy use and low costs; compression on the area of the saphenous vein and of the main collaterals; uniform but moderate pressure on all the limb circumference.