ABSTRACT
Our study was conducted to assess the pharmacokinetics of natural progesterone administered in the novel formula of an effervescent vaginal tablet. Fifty post-menopausal women, with a median age of 43.5 years (range 28-55), volunteered to participate in the research. All women discontinued their hormonal replacement therapy 1 month prior to the study. The pharmacokinetics of 50 and 100 mg of progesterone administered as a vaginal tablet were evaluated. After the initial administration of 50 mg or 100 mg, a mean serum Cmax of 20.43 +/- 8.01 nmol/l and 31.61 +/- 12.62 nmol/l (P < 0.0004) was reached at a Tmax of 6.1 +/- 2.63 and 6.4 +/- 3.35 h respectively. The terminal half-life was 13.18 +/- 1.3 and 13.7 +/- 1.05 h respectively. Continuous use of the 100-mg tablet resulted in a mean serum progesterone concentration of 26.08 +/- 13.96 nmol/l and 21.42 +/- 16.32 nmol/l after 14 and 30 days respectively. Women >40 years were found to have a significantly lower Tmax compared to younger women (P = 0.02). The continuous use of vaginal progesterone did not influence the hormonal, liver or lipid profiles evaluated. Only three (6%) women suffered from mild vaginal irritation. Natural progesterone given as a vaginal tablet is well tolerated, safe and an easily administered treatment. Even in a non-oestrogenized vagina the absorption was efficient and the 100 mg dosage resulted in adequate serum progesterone concentrations.
Subject(s)
Progesterone/administration & dosage , Progesterone/pharmacokinetics , Absorption , Administration, Intravaginal , Adult , Body Mass Index , Female , Half-Life , Humans , Kinetics , Middle Aged , Postmenopause , Progesterone/adverse effects , TabletsABSTRACT
BACKGROUND: Peritoneal ventilation has been shown to be effective in achieving extrapulmonary oxygenation and carbon dioxide elimination in an animal model of severe adult respiratory distress syndrome (ARDS). Cisapride is a "prokinetic" agent (increases gastric emptying), that may increase the splanchnic circulation and thus favourably affect gas exchange in peritoneal ventilation. METHODS: Using Doppler ultrasound the effect of cisapride on the portal venous circulation was examined in eight spontaneously breathing rabbits and the effect of cisapride on gas exchange in five rabbits spontaneously breathing room air was compared with that of a control group who did not receive cisapride. Its effect on gas exchange in five rabbits with ARDS being treated with mechanical lung and peritoneal ventilation was compared with that of a control group, and its effect on gas exchange in five rabbits with ARDS treated with conventional ventilation was also compared with that of a control group. RESULTS: Enteral administration of cisapride increased portal venous blood velocity, as measured ultrasonographically, by a mean of 188% one hour after receiving the drug. In rabbits with ARDS being treated with both peritoneal ventilation and mechanical ventilation to the lungs, those receiving cisapride had arterial oxygen tensions 1.5-3 times that of controls. Cisapride had no effect on arterial blood gas tensions in rabbits who were spontaneously breathing room air, nor in rabbits with ARDS who received only conventional mechanical lung ventilation. CONCLUSIONS: Cisapride increases arterial oxygenation in rabbits with severe ARDS treated with peritoneal ventilation, probably due to its ability to increase splanchnic circulation. It should be considered as an adjuvant medication to peritoneal ventilation.
