The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination rate constant ($\beta$) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the $V_{d}$, $CL_{t}$ and $\beta$ of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.
Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time ($22.5{\pm}10.6hr$) and the mean parasite clearance time ($27.3{\pm}12.2hr$) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P<0.0001). The resistance intensities decreased as follows: chloroquine>piperaquine>pyronarididine>artesunate. The inhibitory dose 50 ($IC_{50}$) was $3.77{\times}10^{-6}mol/L$, $2.09{\times}10^{-6}mol/L$, $0.09{\times}10^{-6}mol/L$, and $0.05{\times}10^{-6}mol/L$, and the mean concentrations for complete inhibition (CIMC) of schizont formation were $5.60{\times}10^{-6}mol/L$, $9.26{\times}10^{-6}mol/L$, $0.55{\times}10^{-6}mol/L$, and $0.07{\times}10^{-6}mol/L$, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.
The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.
Ships need to ensure safety during their navigation, which makes route determination highly important. It must be accompanied by a route following controller that can accurately follow the route. This study proposes a method for automatically generating the ship route based on deep reinforcement learning algorithm and following it using a route following controller. To generate a ship route, under keel clearance was applied to secure the ship's safety and navigation chart information was used to apply ship navigation related regulations. For the experiment, a target ship with a draft of 8.23 m was designated. The target route in this study was to depart from Busan port and arrive at the pilot boarding place of the Ulsan port. As a route following controller, a velocity type fuzzy P ID controller that could compensate for the limitation of a linear controller was applied. As a result of using the deep Q network, a route with a total distance of 62.22 km and 81 waypoints was generated. To simplify the route, the Douglas-Peucker algorithm was introduced to reduce the total distance to 55.67 m and the number of way points to 3. After that, an experiment was conducted to follow the path generated by the target ship. Experiment results revealed that the velocity type fuzzy P ID controller had less overshoot and fast settling time. In addition, it had the advantage of reducing the energy loss of the ship because the change in rudder angle was smooth. This study can be used as a basic study of route automatic generation. It suggests a method of combining ship route generation with the route following control.
Proceedings of the Korea Society of Environmental Toocicology Conference
/
2003.05a
/
pp.189-189
/
2003
Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). To develope as novel anti-allergic drug, kinetic study was performed in rats. Serum concentration of sophoricoside was measured by gas chromatography-mass spectrometry (GC/MS) in male Sprague-Dawley rat (250${\pm}$10g, n=5) after oral administration of sophoricoside (100mg/kg). The recovery of sophoricoside after extraction and concentration was above 95 % from rat serum. Between-day precision(relative standard deviation 2.2-2.8%) and within-day precision(2.0-12.1%) were determined from replicate analysis of a spiked control and incurred serum sample. The detection limits of sophoricoside in this serum was approximately 0.1 ng/mL. The Pharmacokinetic parameters were derived from the noncompartmental analysis. The C$\_$max/(3.56${\pm}$0.34 $\mu\textrm{g}$/mL) value for sophoricoside in male rat was observed at 7.6 h. The elimination half-life(t$\_$1/2/) of sophoricoside was approximately 4.47 h, the mean residence time (MRT) averaged 10.75 h, the total body clearance (Cl) averaged 0.0042 mL/min/kg. and the area under the serum concentration-time curve (AUC$\_$0-$\infty$/) was 24.93 $\mu\textrm{g}$$.$hr/mL.
Han, Sung Hoon;So, Byung Hak;Jung, Won Joong;Kim, Hyung Min
Journal of The Korean Society of Clinical Toxicology
/
v.10
no.2
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pp.111-117
/
2012
Purpose: In Korea, few studies have examined the acute toxicity of anti-obesity drugs. The purpose of this study is to analyze the general characteristics and clinical aspect of acute anti-obesity drug intoxication. Methods: We retrospectively investigated patients admitted to the emergency department after anti-obesity drug intoxication between March, 2004 and February, 2012. The medical records of these patients were reviewed for demographic data, toxicologic history, time elapsed to presentation, clinical symptoms and signs, treatment, and outcome. Results: There were a total of 18 anti-obesity intoxication cases during the study period; of 16 which were included in our study. The purchasing route of the anti-obesity drug was mainly through a doctor's prescription (68.8%), however, some were obtained through the internet and the pharmacies. The mean time to The most commonly ingested antiobesity drug was sibutramine (31.3%) and many of the cases (62.5%) were multi-drug ingestions. The most common clinical manifestations were gastrointestinal symptoms (94%), but, CNS symptoms (75%) and cardiovascular symptoms (75%) were almost equally present. 13 patients (81%) were discharged after clearance of toxic symptoms and signs with a mean observational period of 7.0 hours. 3 patients were admitted for observation and treatment; of which 1 patient died due to fatal complications. Conclusion: Most anti-obesity intoxications show mild toxicity and a nonfatal clinical course. However, the recent trend toward prescribing psychostimulant anti-obesity medication, which can be fatal after an acute overdose, calls physicians' attention to treating of anti-obesity intoxications.
Purpose: Children with cerebral palsy generally have a high incidence of respiratory problem, resulted from poor coughing, airway clearance problem, respiratory muscle weakness, kyphoscoliosis and so forth. The purpose of this study is to investigate the possible factors that can be affected to forced vital capacity (FVC) in children with cerebral palsy. Methods: Total thirty six children with diplegic and hemiplegic cerebral palsy were recruited in this study. They were evaluated by general demographic data (i.e., age, gender, body mass index (BMI)) and variables related to respiratory functions (i.e., chest mobility, waist mobility, maximal phonation time, and maximum inspiratory/expiratory pressure (MIP/MEP)). The correlation between forced vital capacity and the rested variables were analyzed, and multiple regression with stepwise method was conducted to predict respiratory function, in terms of FVC as the dependent variable, and demographic and other respiratory variables as the independent variable. Results: FVC showed a significant correlation with waist mobility (r=0.59, p<0.01), maximal phonation time (r=0.48, p<0.05), MIP (r=0.73, p<0.01), and MEP (r=0.60, p<0.01). In addition, the multiple regression analysis model indicated that FVC could be predicted by the assessment of each waist mobility and MIP. Conclusion: These finding suggest that respiratory function is related to body size and respiratory muscle strength, and that BMI, waist mobility, and MIP can be predictable factors to affected respiratory function in term of FVC.
Two types of water soluble lysine salts of ibuprofen were prepared and evaluated. Physicochemical properties for ibuprofen-l-lysinate (IBL-l), ibuprofen-dl-lysinate (IBL-dl) and ibuprofen (IB) were studied on melting point, specific ratation, UV spectra and $^1H$-NMR spectra. There were not differences between IBL-dl and IBL-l in UV spectra and $^1H$-NMR spectra. The pharmacokinetic parameters of IB were compared to those of its lysine salts (IBL-l and IBL-dl) after i.v. or oral administration at the dose of 50 mg/kg (calculated as IB). Total body clearance ($CL_t$) and area under the plasma concentration-time curve (AUC) were not different between IB group and IBL groups after i.v. administration. On the other hand, IBL-l and IBL-dl produced peak plasma concentrations ($C_{max}$) significantly ealier and higher than IB. Time to reach peak concentration ($T_{max}$) after IBL administration was lower than that after IB administration. There was no difference in AUC across all different groups (IB, IBL-l and IBL-dl) after oral administration. However, absorption rate constant ($k_a$) of IBL-l and IBL-dl were significantly increased than that of IB. These results indicated that the administration of IBL-l and IBL-dl may be advantageous if rapid and reliable onset of pain relief is required.
Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.
The purpose of this study is in the investigation to relieve into the clothing inconvenience levels and to need by arthritis patients who experience clothing difficulties in daily living even without showing conspicuous physical disabilities. For this study, personal interviews were carried out with 151 female arthritis patients, using a questionnaire form consisting of a total of 206 items. Data analysis were done with spss 12.0 for the frequency analysis, cross tab analysis, t-test, and ANOVA. The findings are as follows. 1. The survey subjects were diverse in their age from 20s to 60s and 18.5% of them have need of other's assistance at the time of getting dressed or undressed of clothing. The knee part was felt to be the most uncomfortable, causing the inconveniences in wearing pants or panties. 2. The investigation into the inconvenience levels at the time of dressing or undressing of clothing was indicated that the wearing of pants was the hardest movement to arthritis patients, as the items relating to the movements for putting feet into or pulling them out of pants and those for raising pants over the hip were also accompanied by the feeling of pains. In addition, the aged arthritis patients felt the clothes-wearing movements more difficult. 3. The survey on the kind and inconvenience levels for the clothes currently being worn showed the highest wearing ratio for the pants, which were pointed out to be the most inconvenient. 4. As for the clothing improvement, the needs were located as a whole in the sufficiency in measures of pants crotch and circumference items, the flexibility in materials, the short length of pants, or the front clearance.
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