Pharmacokinetics and preliminary efficacy of two vaginal gel formulations of ultra-low-dose estriol in postmenopausal women.

OBJECTIVES: To investigate the pharmacokinetics, safety and preliminary effectiveness of ultra-low-dose estriol vaginal gel formulations (20 µg/g (T1) and 50 µg/g (T2)) compared to Ovestinon® (estriol 500 µg/0.5 g (R)) and placebo in postmenopausal women. METHODS: Forty-three volunteers were randomly assigned to received T1, T2, R or placebo once daily for 21 days. Absorption of estriol after single and multiple administration was analyzed. Cytological changes in the vagina, tolerability and safety were also investigated. RESULTS: Thirty-six women were included in the pharmacokinetic analysis. Systemic absorption was lower with test formulations (AUC0-t: 171.65 ± 80.18 (T1) and 406.75 ± 199.53 (T2) pg/ml × h) than with Ovestinon® (1221.97 ± 549.06 pg/ml × h). Estriol exposure of the test formulations after multiple administration (AUCss: 36.33 ± 30.52 (T1) and 73.71 ± 46.86 (T2) pg/ml × h) was significantly lower than after single-dose administration and not significantly different between them. In contrast, the exposure after repeated administration of Ovestinon® was considerable and not statistically different from levels after single administration. All estriol formulations produced similar improvement in the vaginal maturation value, while placebo showed a small and not significant change. Overall safety and acceptability were good. CONCLUSIONS: Estriol 20 and 50 µg/g formulations, while showing a comparable capacity for reversing vaginal atrophy, present a highly favorable safety profile, producing a very low systemic absorption of estriol and significantly lower than that of Ovestinon®.

Systemic absorption of rifamycin SV MMX administered as modified-release tablets in healthy volunteers.

The new oral 200-mg rifamycin SV MMX modified-release tablets, designed to deliver rifamycin SV directly into the colonic lumen, offer considerable advantages over the existing immediate-release antidiarrheic formulations. In two pharmacokinetics studies of healthy volunteers, the absorption, urinary excretion, and fecal elimination of rifamycin SV after single- and multiple-dose regimens of the new formulation were investigated. Concentrations in plasma of >2 ng/ml were infrequently and randomly quantifiable after single and multiple oral doses. The systemic exposure to rifamycin SV after single and multiple oral doses of MMX tablets under fasting and fed conditions or following a four-times-a-day (q.i.d.) or a twice-a-day (b.i.d.) regimen could be considered negligible. With both oral regimens, the drug was confirmed to be very poorly absorbable systemically. The amount of systemically absorbed antibiotic excreted by the renal route is far lower than 0.01% of the administered dose after both the single- and multiple-dose regimens. The absolute bioavailability, calculated as the mean percent ratio between total urinary excretion amounts (ΣXu) after a single intravenous injection and after a single oral dose under fasting conditions, was 0.0410±0.0617. The total elimination of the unchanged rifamycin SV with feces was 87% of the administered oral dose. No significant effect of rifamycin SV on vital signs, electrocardiograms, or laboratory parameters was observed.

Internal-external expectancy, maladjustment and psychotherapeutic intervention.

This paper reviewed research on the relationship between internal-external expectancy, maladjustment and psychotherapeutic intervention. The implications drawn from the studies reviewed were: (a) externality is related to poor psychological adjustment and (b) psychotherapy can be effectively utilized to modify expectancy.

A comparison of WISC and WISC-R scoring criteria for comprehension, similarities, and vocabulary responses.

Ten graduate students scored items from the comprehension, similarities, and vocabulary subtests. Five used the WISC manual anf five used the WISC-R manual. Higher percentages of interscorer agreement were obtained from the WISC-R group on all three subtests. An analysis of two-point discrepancies among scorers further supported the superiority of the WISC-R scoring standards over those the WISC.