Bio-mimetic drug delivery systems designed to help the senior population reconstruct melatonin plasma profiles similar to those of the healthy younger population

The secretion of melatonin (MT) is obviously different in the younger and the senior sectors of the population, and the maximum plasma concentration of seniors is only half of that in the younger population group. If exogenous MT can be supplied to senior citizens based on the secretion rate and amount of endogenous MT in the younger population by a bio-mimetic drug delivery system (DDS), an improved therapeutic effect and reduced side effects can be expected. Based upon this hypothesis, the pharmacokinetic parameters of MT, namely, the absorption rate constant (k a), the elimination rate constant (k e), and the ratio of absorption rate (F) to the apparent volume of distribution (V) were obtained by a residual method depending on the plasma concentration curve of immediate release preparations in the healthy younger population. The dose-division method was applied to calculate the cumulative release profiles of MT achieved by oral administration of a controlled release drug delivery system (DDS) to generate plasma MT profiles similar to the physiological level-time profiles. The in vivo release of MT deduced from the healthy younger population physiological MT profiles as the pharmacokinetic output of the bio-mimetic DDS showed a two-phase profile with two different zero order release rates, namely, 4.919 μg/h during 0-4 h (r=0.9992), and 11.097 μg/h during 4-12 h (r=0.9886), respectively. Since the osmotic pump type of DDS generally exhibits a good correlation between in vivo and in vitro release behaviors, an osmotic pump controlled delivery system was designed in combination with dry coating technology targeting on the cumulative release characteristics to mimic the physiological MT profiles in the healthy younger population. The high similarity between the experimental drug release profiles and the theoretical profiles (similarity factor f 2>50) and the high correlation between the predicted plasma concentration profiles and the theoretical plasma concentration profiles (r=0.9366, 0.9163, 0.9264) indicated that a prototype bio-mimetic drug delivery system of MT was established. The similarity factors between the experimental drug release profiles and the theoretical release profile were all larger than 50 both in periods of 0-4 h and 4-12 h, namely, 68.8 and 57.3 for the first batch (Batch No. 20131031), 76.7 and 50.2 for the second batch (Batch No. 20131101), and 73.7 and 51.1 for the third batch (Batch No. 20131126), respectively. The correlation coefficients between the predicted plasma concentration profiles based on the release profiles of the bio-mimetic DDS and physiological profiles were 0.9366 (Batch No. 20131031), 0.9163 (Batch No. 20131101), 0.9264 (Batch No. 20131126), respectively. Since the pharmacokinetic profile of MT in any kind of animal differs markedly from that of human beings, it is impossible to test the bio-mimetic DDS in animals directly. Therefore, the predicted pharmacokinetic profile based upon the in vitro release kinetics is an acceptable surrogate for the conventional animal test. In this research, a bio-mimetic DDS for replacement of MT was designed with in silico evaluation.

Relations of Pulse Wave Velocity to Waist Circumference Independent of Hip Circumference / 한국역학회지

OBJECTIVES: Little is known about the effect of waist circumference (WC) on brachial artery pulse wave velocity (baPWV) independent of hip circumference (HC). Therefore, this study aimed to dissociate specific effect of WC on baPWV independent of HC. METHODS: Of 1,053 rural residents (2004-2005), 777 subjects with no known history of coronary artery diseases or diabetes mellitus over 40 yr were included. To reduce collinearity, we assessed the independent effect of WC with HC on PWV by residual method (WC [RM]). RESULTS: In women, most correlation coefficients were significant between measures of abdominal obesity and baPWV, with the highest (0.32) in waist to hip ratio (WHR), whereas no significance was found in men. All mean values of baPWV among the abdominally obese were higher than those of normal group in women, which were in the order of WHR, WC (RM), and WC. Adjusted OR with 95% CI for baPWV was significantly elevated by increase of WC (RM) upto 4.8 (95% CI: 2.1-11.2), and as 4.3 by WHR (95% CI: 1.6-11.4). CONCLUSION: Considering the difficulty in biologically interpreting WHR, WC (RM) may be a useful indicator of abdominal obesity among females in that it reflects the risk of pulse wave velocity.

Calculation of Pharmacokinetic Parameters and Two-Compartment Model's Parameters by Extravascular Administration Based on Excel Function / 中国药房

OBJECTIVE:To calculate pharmacokinetic parameters and compartment model's parameters by extravascular administration based on Excel function.METHODS:The parameters of pharmacokinetics and compartment model were calculated using residual method and Excel function.RESULTS:Excel can be used to directly demonstrate calculation process of parameters of pharmacokinetics and compartment model,with calculation results in line with those stated in textbooks.CONC-LUSION:The established method is simple,direct-viewing,reliable and easy to be extended,and it can be used to calculate pharmacokinetic parameters in clinical teaching or experiments.