• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.313.1-313.1
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• 2001

• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.5-9
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• 2007

The purpose of this study was to examine the allometric analysis of roxithromycin using pharmacokinetic data. The pharmacokinetic parameters used were $half-life(t_{1/2})$, mean residence time (MRT), clearance (Cl) and volume of distribution at steady state $(V_{ss})$. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula $Y=aW^b$, where 'Y' is $t_{1/2}$, MRT, Cl, or $V_{ss}$, W the body weight and 'a' is an allometric coefficient (intercept) that is constant for a given drug. The exponential term, 'b', is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. As results of the allometric analyses, the logarithms of $t_{1/2}$, MRT, Cl, and $V_{ss}$ were linearly related to the logarithms of body weight. Results of the current analyses could provide information on appropriate doses of roxithromycin for all species.

• Animal cells and systems
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• v.2 no.4
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• pp.477-481
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• 1998

Previous studies have postulated that isometric animals exert similar locomotory capacity (speed, distance) because the amount of energy available for the motion would be the same regardless of body mass (m). To test propriety of this theory, we examined body shape and take-off potential of two frog species, Rana nigromaculata (powerful jumpers) and Bombina orientalis (slow hoppers). Morphological measurements included thigh muscle mass (indicative of total muscle force), hindlimb length (L, determining acceleration distance), and interilial width (shaping take-off motion). To gauge locomotory capacity, take-off speed (v) and take-off angle ($\theta$) were measured from video analyses, and jump distance (R) and take-off Power ($P_{t}$ ) were calculated from equations $R=V^{2}sin2\theta/g$ and ($P_{t}$＝$㎷^{3}/2L$(where g is the gravitational constant). Scaling exponents of morphometric variables for both species were 0.96-1.11 for thigh muscle mass, 0.28-0.29 for hindlimb length, and 0.30-0.36 for interilial width. Scaling exponents of locomotory performance for the two species were -0.01-0.14 for take-off speed, 0.24-0.31 for jump distance, and 0.66-0.84 for take-off power. The results demonstrate that the frogs of this study showed isometric body shape within species, but that take-off response changed allometrically with body mass, indicating that these data did not fully support the previous proposition. An exception was found in take-off speed of B. orientalis, in which the speed changed little with body mass (slope＝-0.01). These findings suggest that the energy availability approach did not properly explain the apparent allometric relations of the take-off response in these animals and that an alternative model such as a power production approach may be worth addressing.

• Journal of Biomedical Engineering Research
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• v.27 no.6
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• pp.323-331
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• 2006

The purpose of this study was to investigate the effect of performing a cognitive task during treadmill walking on the stride rate variability. Ten university students(age $24.0{\pm}0.25$, height $172{\pm}3.1cm$, weight $66{\pm}5.3kg$) were participated in dual task experiments which consist of both walking alone and walking with a cognitive task. Two-back task was selected for the cognitive task since it did not have learning effect during the experimental procedure.3D motion analysis system was used to measure subject's position data by changing walking speed with 4.8, 5.6, 6.4, 6.8, and 7.2 km/hr. Stride rate was calculated by the time between heel contact and heel contact. Accuracy rate of a cognitive task during walking, coefficient of variance, allometric scaling methods and Fano factor were used to estimated the stride rate variability. As the walking speed increased, accuracy rate decreased and the logarithmic value of Fano factor increased which showed the statistical difference. Thus it can be concluded that the gait control mechanism is distracted by the secondary attention focus which is the cognitive task ie. two-back task. Further study is needed to clarify this by increasing the number of subject and experiment time.