• Title/Summary/Keyword: pharmacodynamic

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Effect of Food on Pharmacokinetics and Pharmacodynamics of Fenofibric Acid after a Single Oral Dose of Fenofibrate Sustained-Release Capsule (식단에 따르는 페노피브레이트 서방성 캡슐의 1회 경구 투여 후 약물동태학 및 약물동력학의 평가)

  • Yun, Hwi-yeol;Kim, Joung-hyun;Lee, Eun Joo;Chung, Soo Youn;Choi, Sun-oK;Kim, Hyung Kee;Kwon, Jun-tack;Kang, Wonku;Kwon, Kwang-il
    • Korean Journal of Clinical Pharmacy
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    • v.15 no.1
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    • pp.34-40
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    • 2005
  • We examined the effects of food on pharmacokinetic and pharmacodynamic properties of fenofibrate released from sustained-release(SR) capsule as therapy for hypolipidemia. Twenty-four healthy volunteers were used in $3{\times}3$ crossover pharmacokinetic and pharmacodynamic study; Additional six volunteers were used as a control group (i.e., no fenofibrate administration). A single dose of fenofibrate (SR capsule, 250 mg) was administered on three occasions: after overnight fasting, after consumption of a standard breakfast, and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high performance liquid chromatography, and pharmacokinetic parameters were calculated using ADAPT II program. Plsama triglyceride concentrations were measured by blood chemistry analyzer (CH-100). The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than did the standard breakfast and fasted conditions. Plasma concentrations of triglyceride at 24 hours decreased significantly after the administration of fenofibrate compared with the concentration at 0 hours(P<0.05). In healthy volunteers, the bioavailability of fenofibrate was greater when administered via sustained-release capsules immediately after the consumption of food than after fasting condition.

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Quantitative analysis of the effect of fraction of inspired oxygen on peripheral oxygen saturation in healthy volunteers

  • Kang, Bong Jin;Kim, Myojung;Bang, Ji-Yeon;Lee, Eun-Kyung;Choi, Byung-Moon;Noh, Gyu-Jeong
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.20 no.2
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    • pp.73-81
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    • 2020
  • Background: The international organization for standardization (ISO) 80601-2-61 dictates that the accuracy of a pulse oximeter should be assessed by a controlled desaturation study. We aimed to characterize the relationship between the fraction of inspired oxygen (FiO2) and peripheral oxygen saturation (SpO2) using a turnover model by retrospectively analyzing the data obtained from previous controlled desaturation studies. Materials and Methods: Each volunteer was placed in a semi-Fowler's position and connected to a breathing circuit to administer the hypoxic gas mixture containing medical air, oxygen, nitrogen, and carbon dioxide. Volunteers were exposed to various levels of induced hypoxia over 70-100% arterial oxygen saturation (SaO2). The study period consisted of two rounds of hypoxia and the volunteers were maintained in room air between each round. FiO2 and SpO2 were recorded continuously during the study period. A population pharmacodynamic analysis was performed with the NONMEM VII level 4 (ICON Development Solutions, Ellicott City, MD, USA). Results: In total, 2899 SpO2 data points obtained from 20 volunteers were used to determine the pharmacodynamic characteristics. The pharmacodynamic parameters were as follows: kout = 0.942 1/min, Imax = 0.802, IC50 = 85.3%, γ = 27.3. Conclusion: The changes in SpO2 due to decreases in FiO2 well explained by the turnover model with inhibitory function as a sigmoidal model.

Methods for Pharmacodynamic Analysis and Proposed Protocols for Bioequivalence Study of Acarbose (Acarbose 제제의 약력학적 평가 및 생물학적동등성 시험법에 대한 연구)

  • Bae, Jung-Woo;Jang, Choon-Gon;Lee, Seok-Yong
    • YAKHAK HOEJI
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    • v.51 no.6
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    • pp.440-446
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    • 2007
  • Arcabose is a competitive inhibitor of the intestinal ${\alpha}$-glucosidases and reduces the postprandial digestion and absorption of carbohydrate and disaccharides. Due to its negligible oral absorption, measuring drug concentration in the plasma is impractical. Thus, the common pharmacokinetic study is not available to determine the bioequivalence of the generic acarbose preparations. The aim of this study is the establishment of pharmacodynamic assessment method for the bioequivalence test of the generic acarbose preparations. Placebo-controlled cross-over ($3{\times}3$) clinical study was conducted in 23 healthy volunteers. Volunteers received a single oral dose of placebo, reference drug ($Glucoby^{(R)}$ 100 mg, Lot # D043) or test drug ($Glucoby^{(R)}$ 100 mg, Lot # E005) just before breakfast, then blood samples for evaluation of serum glucose and insulin levels were taken during for 4 hours. $C_{max},\;AUC_{0-2},\;AUC_{0-4},\;{\Delta}C_{max},\;{\Delta}AUC_{0-2}\;and\;{\Delta}AUC_{0-4}$ of the postprandial plasma glucose level significantly decreased when a single dose of acarbose 100 mg preparations was administered. However, any significant difference was not detected between the groups taken the reference drug and the test drug. These results proposed that the pharmacodynamic protocols of this study is suitable to use for bioequivalence test of acarbose preparations. On the basis of the results of this study and the data of literature on this subject, the standard protocols of bioequivalence study of acarbose preparation are proposed.

Modified Pharmacokinetic/Pharmacodynamic model for electrically activated silver-titanium implant system

  • Tan, Zhuo;Orndorff, Paul E.;Shirwaiker, Rohan A.
    • Biomaterials and Biomechanics in Bioengineering
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    • v.2 no.3
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    • pp.127-141
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    • 2015
  • Silver-based systems activated by low intensity direct current continue to be investigated as an alternative antimicrobial for infection prophylaxis and treatment. However there has been limited research on the quantitative characterization of the antimicrobial efficacy of such systems. The objective of this study was to develop a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model providing the quantitative relationship between the critical system parameters and the degree of antimicrobial efficacy. First, time-kill curves were experimentally established for a strain of Staphylococcus aureus in a nutrientrich fluid environment over 48 hours. Based on these curves, a modified PK/PD model was developed with two components: a growing silver-susceptible bacterial population and a depreciating bactericidal process. The test of goodness-of-fit showed that the model was robust and had good predictability ($R^2>0.7$). The model demonstrated that the current intensity was positively correlated to the initial killing rate and the bactericidal fatigue rate of the system while the anode surface area was negatively correlated to the fatigue rate. The model also allowed the determination of the effective range of these two parameters within which the system has significant antimicrobial efficacy. In conclusion, the modified PK/PD model successfully described bacterial growth and killing kinetics when the bacteria were exposed to the electrically activated silver-titanium implant system. This modeling approach as well as the model itself can also potentially contribute to the development of optimal design strategies for other similar antimicrobial systems.

Pharmacokinetic-Pharmacodynamic Modeling for the Relationship between Glucose-Lowering Effect and Plasma Concentration of Metformin in Volunteers

  • Lee, Shin-Hwa;Kwon, Kwang-il
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.806-810
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    • 2004
  • Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection

  • Luo, Wanhe;Wang, Dehai;Qin, Hua;Chen, Dongmei;Pan, Yuanhu;Qu, Wei;Huang, Lingli;Xie, Shuyu
    • Journal of Veterinary Science
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    • v.22 no.6
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    • pp.41.1-41.14
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    • 2021
  • Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC0-24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation. The dose was calculated based on the AUC0-24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 ㎍/mL, 811.99 ± 54.70 ㎍·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 ㎍/mL, 735.85 ± 26.20 ㎍·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 ㎍/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC0-24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions: A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.