Semagacestat pharmacokinetics are not significantly affected by formulation, food, or time of dosing in healthy participants.

Semagacestat, a γ-secretase inhibitor, reduces formation of amyloid beta peptide. Two single-dose (140 mg), open-label, randomized, 3-period, crossover studies evaluated the effect of formulation, food, and time of dosing on the pharmacokinetics and pharmacodynamics of semagacestat in healthy participants. The first study (n = 14) compared tablet to capsules. For all formulations, the median time to maximum plasma concentration (t(max)) was generally 1.0 hour. Plasma elimination was rapid, with a half-life of approximately 2.5 hours. Tablet form II bioavailability (F) relative to capsule was approximately 100% (F = 1.03 [90% confidence interval (CI), 0.96-1.10]). In the second study, participants (n = 27) received semagacestat either fed or fasting in the morning or fasting in the evening. No significant change in exposure (AUC(0-∞) [area under the concentration-time curve from 0 to infinity] ratio = 1.02, [90% CI, 0.990-1.05]) occurred with food, whereas maximum plasma concentration (C(max)) declined approximately 15%, and median t(max) was delayed to 1.5 hours. Time of dosing made no significant difference in AUC(0-∞), C(max), or t(max) (AUC(0-∞) ratio 1.01, [90% CI, 0.975-1.04]). No clinically significant safety concerns occurred in either study. Accordingly, semagacestat may be dosed without regard to formulation, food, or time of administration.

Proximate nutrient analyses of four species of submerged aquatic vegetation consumed by Florida manatee (Trichechus manatus latirostris) compared to romaine lettuce (Lactuca sativa var. longifolia).

Free-ranging Florida manatees (Trichechus manatus latirostris) consume a variety of sea grasses and algae. This study compared the dry matter (DM) content, proximate nutrients (crude protein [CP], ether-extracted crude fat [EE], nonfiber carbohydrate [NFC], and ash), and the calculated digestible energy (DE) of sea grasses (Thalassia testudinum, Halodule wrightii, and Syringodium filiforme) collected in spring, summer, and winter, and an alga (Chara sp.) with those of romaine lettuce (Lactuca sativa var. longifolia). Neutral-detergent fiber (NDF), acid-detergent fiber (ADF), and lignin (L) measured after ash-extraction were also compared. Results of statistical tests (C = 0.01) revealed DM content was higher in aquatic vegetation than in lettuce (P = 0.0001), but NDF and ADF were up to threefold greater, EE (P = 0.00001) and CP (P = 0.00001) were 2-9 times less, and NFC (P = 0.0001) was 2-6 times lower in sea grass than in lettuce, on a DM basis. Chara was lower in NDF, ADF, L, EE, CP, and NFC relative to lettuce on a DM basis. Ash content (DM basis) was higher (P = 0.0001), and DE was 2-6 times lower in aquatic vegetation than in lettuce. Sea grass rhizomes had lower L and higher ash contents (DM basis) than sea grass leaves. Based on the nutrient analyses, romaine lettuce and sea grasses are not equivalent forages, which suggests that the current diet of captive Florida manatees should be reassessed.

Particle diffusional layer thickness in a USP dissolution apparatus II: a combined function of particle size and paddle speed.

This work was to investigate the effects of particle size and paddle speed on the particle diffusional layer thickness h(app) in a USP dissolution apparatus II. After the determination of the powder dissolution rates of five size fractions of fenofibrate, including <20, 20-32, 32-45, 63-75, and 90-106 microm, the present work shows that the dependence of h(app) on particle size follows different functions in accordance with the paddle speed. At 50 rpm, the function of h(app) is best described by a linear plot of h{app} = 9.91sqrt d-23.31 (R(2) = 0.98) throughout the particle diameter, d, from 6.8 to 106 microm. In contrast, at 100 rpm a transitional particle radius, r, of 23.7 microm exists, under which linear relationship h(app) = 1.59r (R(2) = 0.98) occurs, but above which h(app) becomes a constant of 43.5 microm. Thus, h(app) changes not only with particle size, but also with the hydrodynamics under standard USP configurations, which has been overlooked in the past. Further, the effects of particle size and paddle speed on h(app) were combined using dimensionless analysis. Within certain fluid velocity/particle regime, linear correlation of h(app)/d with the square-root of Reynolds number (d\varpi/upsilon){1/2}, that is, h{app}/d = 1.5207 - 9.25 x 10{- 4} (d\varpi/n){1/2} (R(2) = 0.9875), was observed.