Pharmacokinetics and safety of low-dose submicron indomethacin 20 and 40 mg compared with indomethacin 50 mg.

INTRODUCTION: Indomethacin is a potent analgesic that, similar to other nonsteroidal anti-inflammatory drugs, is associated with serious dose-related adverse events. There is a need for newer nonsteroidal anti-inflammatory drug products with improved tolerability. Low-dose submicron indomethacin was developed using SoluMatrix Fine Particle Technology™ to enable treatment at lower doses than commercially available indomethacin drug products. This study evaluated the pharmacokinetics and safety of submicron indomethacin 20 and 40 mg compared with indomethacin 50-mg capsules. METHODS: This was a phase 1, randomized, open-label, 4-period, 4-sequence, single-dose crossover study. Forty healthy volunteers received low-dose submicron indomethacin 20- or 40-mg capsules, or indomethacin 50-mg capsules under fasting or fed conditions. Pharmacokinetic parameters and safety were assessed. RESULTS: Comparable fasting peak plasma levels (mean ± standard deviation) were demonstrated for submicron indomethacin 40 mg (2368.79 ± 631.38 ng/ml) and indomethacin 50 mg (2369.40 ± 969.06 ng/ml). The overall systemic exposure (geometric least squares mean; 95% CI) was > 21% lower for submicron indomethacin 40 mg (6007.71 ng·h/mL; 5585.73-6461.58) compared with indomethacin 50 mg (7646.23 ng·h/ml; 7110.44-8222.40) under fasting conditions. Food delayed the rate but did not affect the extent of indomethacin absorption from submicron indomethacin 40 mg. Submicron indomethacin 40 mg administration resulted in earlier time to peak plasma levels (median 1.67; min-max 0.5-3.5 hours) under fasting conditions compared with indomethacin 50 mg (2.02; 0.5-5.0 hours). Submicron indomethacin 20 and 40 mg were dose proportional and generally well tolerated. CONCLUSION: Compared with indomethacin 50 mg, submicron indomethacin 40 mg achieved similar peak plasma concentrations, lower systemic exposure, and a faster time to peak plasma concentration, indicating rapid absorption. The current formulation of low-dose submicron indomethacin has recently demonstrated efficacy in 2 phase 3 studies in patients with acute pain following bunionectomy and represents a new, low-dose treatment option for patients with acute pain.

Socio-economic differences in food group and nutrient intakes among young women in Ireland.

The present study aimed to investigate socio-economic disparities in food and nutrient intakes among young Irish women. A total of 221 disadvantaged and seventy-four non-disadvantaged women aged 18-35 years were recruited. Diet was assessed using a diet history protocol. Of the total population, 153 disadvantaged and sixty-three non-disadvantaged women were classified as plausible dietary reporters. Food group intakes, nutrient intakes and dietary vitamin and mineral concentrations per MJ of energy consumed were compared between the disadvantaged and non-disadvantaged populations, as was compliance with dietary fibre, macronutrient and micronutrient intake guidelines. The disadvantaged women had lower intakes than the non-disadvantaged women of fruit, vegetables, fish, breakfast cereals, low-fat milk and wholemeal bread (all P< 0·001), yogurt (P= 0·001), low-fat spread (P= 0·002) and fresh meat (P= 0·003). They also had higher intakes of butter, processed red meats, white bread, sugar-sweetened beverages, fried potatoes and potato-based snacks (all P< 0·001) and full-fat milk (P= 0·014). Nutritionally, the disadvantaged women had higher fat, saturated fat and refined sugar intakes; lower dietary fibre, vitamin and mineral intakes; and lower dietary vitamin and mineral densities per MJ than their more advantaged peers. Non-achievement of carbohydrate (P= 0·017), fat (P< 0·001), saturated fat (P< 0·001), refined sugar (P< 0·001), folate (P= 0·050), vitamin C (P< 0·001), vitamin D (P= 0·047) and Ca (P= 0·019) recommendations was more prevalent among the disadvantaged women. Both groups showed poor compliance with Fe and Na guidelines. We conclude that the nutritional deficits present among these socially disadvantaged women are significant, but may be potentially ameliorated by targeted food-based interventions.

Sex-biased dispersal and natal philopatry in the diamondback terrapin, Malaclemys terrapin.

Nesting ecology and population studies indicate that diamondback terrapins (Malaclemys terrapin) exhibit nest site fidelity and high habitat fidelity. However, genetic studies indicate high levels of gene flow. Because dispersal affects the genetics and population dynamics of a species, we used six highly polymorphic microsatellite markers to investigate sex-biased dispersal and natal philopatry of M. terrapin in Barnegat Bay, NJ. We compared results of spatial autocorrelation analysis, assignment methods and Wright's F(ST) estimators to a mark-recapture analysis. Mark-recapture analysis over a 4-year period indicated that most individuals have relatively small home ranges (<2 km), with mature females displaying greater home ranges than males. Goodness of fit analysis of our mark-recapture study indicated that some juvenile males were likely transient individuals moving through our study location. Mean assignment indices and first-generation migrant tests indicated that mature males were more prone to disperse than mature females, but first-generation migrant tests indicated that per capita there are more female than male dispersers. Thus, the relative importance of males and females on gene flow in terrapin populations may change in relation to population sex ratios. Spatial autocorrelation analysis indicated that mature females exhibited natal philopatry to nesting beaches, but first-generation migrant tests indicated that a small number of females failed to nest on natal beaches. Finally, we discuss the important conservation implications of male-biased dispersal and natal philopatry in the diamondback terrapin.