scholarly journals Pharmacokinetic Study of Anti-osteoarthritic Compounds of a Standardized Fraction from Sphaeralcea Angustifolia

2021 ◽  
Vol 14 (7) ◽  
pp. 610
Author(s):  
Jade Serrano-Román ◽  
Pilar Nicasio-Torres ◽  
Elizabeth Hernández-Pérez ◽  
Enrique Jiménez-Ferrer
Keyword(s):  
High Performance ◽  
Compartment Model ◽  
Information Criteria ◽  
Time Range ◽  
Suspension Cell Culture ◽  
Inflammatory Conditions ◽  
Two Compartment Model ◽  
Use Of Knowledge ◽  
Pharmacokinetic Assay ◽  
Pharmacokinetic Behavior

Sphaeralcea angustifolia has been widely used in inflammatory conditions such as blows, bruises, fractures, and wounds. The compounds identified as active in plants and suspension cell culture of S. angustifolia were tomentin, scopoletin, and sphaeralcic acid. To consolidate the integral use of knowledge about the S. angunstifolia and strengthen its pharmacological use in patients with knee osteoarthritis, the pharmacokinetic behavior of the active compounds was characterized. The SaTSS (S. angustifoloia standardized in Tomentin, Scopoletin, and Sphaeralcic acid) anti-ostearthritic fraction was obtained from cell suspension. The analytical method of High-Performance Liquid Chromatography (HPLC) for tomentin, scopoletin, and sphaeralcic acid were validated determining the accuracy, precision linearity, sensibility, specificity, detection limits, and quantification time-range parameters, as well as extraction efficiency and stability of compounds. The pharmacokinetic assay was performed with ICR mice strain, in which the mice were administrated with a single oral or intravenous dose (400 mg/kg with 7.1 mg/kg of scopoletin and tomentin in mixture and 34.6 mg/kg of sphaeralcic acid) of the SaTSS standardized active fraction. The results of the validated analytical methods allowed establishing, in a validated manner, that a coumarin mixture and sphaeralcic acid present in the SaTES fraction were detected in plasma. According to the values of Akaike Information Criteria (AIC), Sum of Squares (SS), Schwarz Criteria (SC), and by the determination coefficient (R2), the compounds follow a two-compartment model.

scholarly journals 1573. Population Pharmacokinetic Analyses for Cefepime in Adult and Pediatric Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S574-S575
Author(s):  
Jiajun Liu ◽  
Michael Neely ◽  
Jeffrey Lipman ◽  
Fekade B Sime ◽  
Jason Roberts ◽  
...  
Keyword(s):  
Rate Constant ◽  
Pediatric Patients ◽  
Validation Cohort ◽  
External Validation ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Information Criteria ◽  
Population Pharmacokinetic ◽  
Final Model ◽  
Two Compartment Model

Abstract Background Cefepime (CEF) is commonly used for adult and pediatric infections. Several studies have examined CEF’s pharmacokinetics (PK) in various populations; however, a unifying PK model for adult and pediatric subjects does not yet exist. We developed a combined population model for adult and pediatric patients and validated the model. Methods The initial model includes adult and pediatric patients with a rich cefepime sampling design. All adults received 2 g CEF while pediatric subjects received a mean of 49 (SD 5) mg/kg. One- and two-compartment models were considered as base models and were fit using a non-parametric adaptive grid algorithm within the Pmetrics package 1.5.2 (Los Angeles, CA) for R 3.5.1. Compartmental model selection was based on Akaike information criteria (AIC). Covariate relationships with PK parameters were visually inspected and mathematically assessed. Predictive performance was evaluated using bias and imprecision of the population and individual prediction models. External validation was conducted using a separate adult cohort. Results A total of 45 subjects (n = 9 adults; n = 36 pediatrics) were included in the initial PK model build and 12 subjects in the external validation cohort. Overall, the data were best described using a two-compartment model with volume of distribution (V) normalized to total body weight (TBW/70 kg) and an allometric scaled elimination rate constant (Ke) for pediatric subjects (AIC = 4,138.36). Final model observed vs. predicted plots demonstrated good fit (population R2 = 0.87, individual R2 = 0.97, Figure 1a and b). For the final model, the population median parameter values (95% credibility interval) were V0 (total volume of distribution), 11.7 L (10.2–14.6); Ke for adult, 0.66 hour−1 (0.38–0.78), Ke for pediatrics, 0.82 hour−1 (0.64–0.85), KCP (rate constant from central to peripheral compartment), 1.4 hour−1 (1.3–1.8), KPC (rate constant from peripheral to central compartment), 1.6 hour−1 (1.2–1.8). The validation cohort has 12 subjects, and the final model fit the data well (individual R2 = 0.75). Conclusion In this diverse group of adult and pediatrics, a two-compartment model described CEF PK well and was externally validated with a unique cohort. This model can serve as a population prior for real-time PK software algorithms. Disclosures All authors: No reported disclosures.

scholarly journals Compartmental Pharmacokinetic Analysis of Oral Amprenavir with Secondary Peaks

2007 ◽  
Vol 51 (5) ◽  
pp. 1822-1826 ◽  
Author(s):  
Olanrewaju Okusanya ◽  
Alan Forrest ◽  
Robin DiFrancesco ◽  
Sanela Bilic ◽  
Susan Rosenkranz ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Information Criteria ◽  
Secondary Peak ◽  
Pharmacokinetic Analysis ◽  
Therapeutic Drug ◽  
Healthy Human ◽  
Two Compartment Model

ABSTRACT Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043. Serial blood samples were obtained over 24 h. Samples were analyzed for amprenavir and fit to a compartmental model using ADAPT II software, with all relevant parameters conditional with respect to bioavailability. The model accommodated secondary peaks by incorporating clearance out of the central compartment with delayed instantaneous release back into the gut compartment. The data were weighted by the inverse of the estimated measurement error variance; model discrimination was determined using Akaike's Information Criteria. A total of 76 subjects were evaluable in the study analysis. The data were best fit by a two-compartment model, with 98.7% of the subjects demonstrating a secondary peak. Amprenavir had a mean total clearance of 1.163 liters/h/kg of body weight (0.7), a central volume of distribution of 1.208 liters/kg (0.8), a peripheral volume of distribution of 8.2 liters/kg (0.81), and distributional clearance of 0.04 liters/h/kg (0.81). The time to the secondary peak was 7.86 h (0.17), and clearance into a recycling compartment was 0.111 liters/kg/h (0.74). Amprenavir pharmacokinetics has been well described using a two-compartment model with clearance to a recycling compartment and release back into the gut. The nature of the secondary peaks may be an important consideration for the interpretation of amprenavir plasma concentrations during therapeutic drug monitoring.

scholarly journals Comparison of different kinetic models for dynamic 68Ga-FAPI-04 PET/CT imaging of hepatocellular carcinoma with various, also dual-blood input function

2020 ◽  
Author(s):  
Barbara Katharina Geist ◽  
Haiqun Xing ◽  
Jingnan Wang ◽  
Ximin Shi ◽  
Haitao Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinetic Parameters ◽  
Dynamic Model ◽  
Kinetic Models ◽  
Compartment Model ◽  
Input Function ◽  
Information Criteria ◽  
Model Parameters ◽  
Time Activity ◽  
Two Compartment Model

Abstract Aim: The aim of the study is to establish a 68Ga-FAPI-04 dynamic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions.Methods: 68Ga-FAPI-04 PET dynamic images of 7 HCC lesions and 5 non-HCC lesions from 8 patients were analyzed from their time-activity curve (TACs). Five kinetic models were applied to the TACs, using hepatic artery and/or portal vein as input functions. Results were analyzed according to Akaike and Schwartz information criteria.Results: A two-compartment model using solely a venous input function was most preferred and showed significant differences between healthy regions and lesions in almost all model parameters. Using a two-compartment model with one arterial input function delivered significant differences between HCC and non-HCC regions in the case of K1 (p = 0.03).Conclusion: The established FAPI PET dynamic model in liver lesions suggested that FAPI PET kinetic parameters have the potential to differentiate between HCC and non-HCC lesions.

scholarly journals Pharmacokinetics and Efficacy of Piperaquine and Chloroquine in Melanesian Children with Uncomplicated Malaria

2007 ◽  
Vol 52 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Harin A. Karunajeewa ◽  
Kenneth F. Ilett ◽  
Ivo Mueller ◽  
Peter Siba ◽  
Irwin Law ◽  
...  
Keyword(s):  
Half Life ◽  
Uncomplicated Malaria ◽  
Active Metabolite ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Median Volume ◽  
Intensive Sampling

ABSTRACT The disposition of chloroquine (CQ) and the related 4-aminoquinoline, piperaquine (PQ), were compared in Papua New Guinean children with uncomplicated malaria. Twenty-two children were randomized to 3 days of PQ phosphate at 20 mg/kg/day (12 mg of PQ base/kg/day) coformulated with dihydroartemisinin (DHA-PQ), and twenty children were randomized to 3 days of CQ at 10 mg base/kg/day with a single dose of sulfadoxine-pyrimethamine (CQ-SP). After a 42-day intensive sampling protocol, PQ, CQ, and its active metabolite monodesethyl-chloroquine (DECQ) were assayed in plasma by using high-performance liquid chromatography. A two-compartment model with first-order absorption was fitted to the PQ and CQ data. There were no significant differences in age, gender, body weight, or admission parasitemia between the two groups. The PCR-corrected 42-day adequate clinical and parasitological responses were 100% for DHA-PQ and 94% for CQ-SP, but P. falciparum reinfections during follow-up were common (33 and 18%, respectively). For PQ, the median volume of distribution at steady state, allowing for bioavailability (V ss/F), was 431 liters/kg (interquartile range [IQR], 283 to 588 liters/kg), the median clearance (CL/F) was 0.85 liters/h/kg (IQR, 0.67 to 1.06 liters/h/kg), the median distribution half-life (t 1/2 α) was 0.12 h (IQR, 0.05 to 0.66 h), and the median elimination half-life (t 1/2 β) was 413 h (IQR, 318 to 516 h). For CQ, the median V ss/F was 154 liters/kg (IQR, 101 to 210 liters/kg), the median CL/F was 0.80 liters/h/kg (IQR, 0.52 to 0.96 liters/h/kg), the median t 1/2 α was 0.43 h (IQR, 0.05 to 1.82 h), and the median t 1/2 β was 233 h (IQR, 206 to 298 h). The noncompartmentally derived median DECQ t 1/2 β was 290 h (IQR, 236 to 368 h). Combined molar concentrations of DECQ and CQ were higher than those of PQ during the elimination phase. Although PQ has a longer t 1/2 β than CQ, its prompt distribution and lack of active metabolite may limit its posttreatment malaria-suppressive properties.

An Experimental Pharmacokinetics Study of Diazepam and Its Metabolites in Oral Fluid of Chinese Population

2020 ◽  
Vol 44 (4) ◽  
pp. 348-353
Author(s):  
Le-le Wang ◽  
Xin-xin Ren ◽  
Yi He ◽  
Guan-feng Cui ◽  
Zhi-wen Wei ◽  
...  
Keyword(s):  
Chinese Population ◽  
High Performance ◽  
Oral Fluid ◽  
Solid Phase ◽  
Compartment Model ◽  
Tandem Mass ◽  
Spectrometry Method ◽  
Chromatography Tandem Mass Spectrometry ◽  
Two Compartment Model ◽  
Liquid Chromatography Tandem Mass

Abstract Diazepam abuse is widespread all over the word, leading to an increasing number of forensic cases such as suicide, drug-driving and robbery, but relevant studies are limited regarding the extraction of diazepam and its metabolites in oral fluid. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites in oral fluid after a single oral dose in healthy volunteers. There was a total of 28 volunteers, and each ingested 5 mg diazepam orally, then ~2 mL oral fluid were collected from each participant at post-consumption time-points of prior (zero), 1, 2, 4, 8, 12, 24 h and 2, 3, 6, 12 and 15 days, respectively. All samples were extracted with solid-phase extraction and analyzed with high-performance liquid chromatography-tandem mass spectrometry method, and diazepam and nordazepam were detected in the oral fluid of volunteers. Pharmacokinetics of diazepam in oral fluid conformed to a two-compartment model, and k01_HL, k12_HL, k10_HL were 0.7 ± 1.1, 31.4 ± 68.5, 12.1 ± 11.6 h, respectively, nordazepam conformed to an one-compartment model, and k01_HL, k10_HL were 41.5 ± 44.8, 282.3 ± 365.5 h, respectively. Both diazepam and nordazepam could be detected continuously for 15 days, although there were individual differences, and the results regarding diazepam detecting in oral fluid will be of much help in forensic science and drug screening filed.

scholarly journals Intravitreal, Retinal, and Central Nervous System Foscarnet Concentrations after Rapid Intravenous Administration to Rabbits

2000 ◽  
Vol 44 (3) ◽  
pp. 756-759 ◽  
Author(s):  
Luis F. López-Cortés ◽  
R. Ruiz-Valderas ◽  
M. J. Lucero-Muñoz ◽  
E. Cordero ◽  
M. T. Pastor-Ramos ◽  
...  
Keyword(s):  
High Performance ◽  
Compartment Model ◽  
Vitreous Humor ◽  
Pharmacokinetic Analysis ◽  
Time Curve ◽  
Concentration Time ◽  
Two Compartment Model ◽  
Good Penetration ◽  
Csf Levels ◽  
Pigmented Rabbits

ABSTRACT Retinal, vitreous humor, brain, and cerebrospinal fluid (CSF) foscarnet levels were measured by high-performance liquid chromatography after administration of an intravenous dose of 120 mg/kg of body weight to 32 pigmented rabbits. A pharmacokinetic analysis was done using a two-compartment model. The penetration ratios, defined as ratios of retinal, vitreous humor, brain, and CSF areas under the concentration-time curve from 0 to 2 h were 110% ± 1%, 12.3% ± 0.7%, 118% ± 1%, and 20.2% ± 2.2%, respectively. These results suggest a good penetration of foscarnet into the retinal and brain tissues, reaching higher concentrations than those estimated from vitreous humor and CSF levels.

scholarly journals Assessment of Micafungin Dosage Regimens in Patients with Cancer Using Pharmacokinetic/Pharmacodynamic Modeling and Monte Carlo Simulation

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1363
Author(s):  
Saeed Alqahtani ◽  
Asma Alfarhan ◽  
Abdullah Alsultan ◽  
Emad Alsarhani ◽  
Abdulaziz Alsubaie ◽  
...  
Keyword(s):  
High Performance ◽  
Compartment Model ◽  
Pharmacodynamic Modeling ◽  
Pharmacokinetic Parameters ◽  
Candida Spp ◽  
Patients With Cancer ◽  
Treatment And Prevention ◽  
Two Compartment Model ◽  
Linear Elimination ◽  
Empirical Antifungal Therapy

Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer.

Two-Compartment Model of Cholesterol Kinetics for Establishment of Treatment Strategy of LDL Apheresis in Nephrotic Hypercholesterolemia

1994 ◽  
Vol 12 (6) ◽  
pp. 317-326 ◽  
Author(s):  
Masatomo Yashiro ◽  
Eri Muso ◽  
Munehiro Matsushima ◽  
Ryoichi Nagura ◽  
Kenji Sawanishi ◽  
...  
Keyword(s):  
Treatment Strategy ◽  
Compartment Model ◽  
Ldl Apheresis ◽  
Two Compartment Model

Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man

1983 ◽  
Vol 64 (2) ◽  
pp. 207-212 ◽  
Author(s):  
S. L. Grainger ◽  
P. W. N. Keeling ◽  
I. M. H. Brown ◽  
J. H. Marigold ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Accurate Determination ◽  
Liver Blood Flow ◽  
Compartment Model ◽  
Hepatic Extraction ◽  
Non Invasive ◽  
Two Compartment Model ◽  
Hepatic Extraction Ratio ◽  
Plasma Disappearance Curve

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.

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