scholarly journals PHARMACOKINETIC STUDY OF BEDAQUILINE AMONG INDIAN MDR-TB PATIENTS IN CLINICAL SETTINGS

2021 ◽  
Author(s):  
Vamshikrishna Gone ◽  
Shalini Thakur ◽  
Nithya Valupadasu ◽  
Yashaswini Akoju ◽  
Bhuvana Chandra Pasupuleti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Routine Clinical Practice ◽  
Multi Drug Resistance ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Clinical Settings ◽  
Diseased Person ◽  
Mdr Tb ◽  
Us Fda

Bedaquiline, a novel drug was approved for the treatment of multi-drug resistance tuberculosis (MDR-TB) by the US FDA in 2012. It is majorly caused because of the transmission of multi-resistant strain from a diseased person to a healthy individual and by genetic factors. Safety, efficacy, and bactericidal activity of Bedaquiline were reported in various studies, but the pharmacokinetic analysis of Bedaquiline in clinical settings was unclear. This study serves as evidence for the physicians regarding the pharmacokinetic data and managing drug therapy and for better patient outcome in routine clinical practice. This study is conducted in a total of 58 patients with newly diagnosed, smear-positive, MDR-TB patients who received Bedaquiline as per RNTCP guidelines. Plasma samples were collected after the Bedaquiline administration. The patient samples were analyzed. The pharmacokinetic data were drawn by using software kinetic-2000, version 5.03.The observed Cmax was 2523.08 ng/mL, Tmax was reached at 4 hrs, AUC(0-24) was 21727.1 ng *hr/mL, AUMC (0-24) was 222953.8 ng *hr2/mL. Whereas the half-life of the drug was found at 7 .02 hrs and mean residence time (MRT) was found to be 10.25 hrs respectively. The data was even on the 14th day of therapy. The Cmax is shown to be 5937.1ng/mL reaching the Cmax at about 5 hours. While the AUC(0-24) was found to be 65780 ng *hr/mL. Conclusively, pharmacokinetic parameters were evaluated and found to be within the desired limits with minimal changes. This method can be further used for the quantification of Bedaquiline in routine clinical practice.

The Influence of Different Disease States on Rituximab Pharmacokinetics

2020 ◽  
Vol 21 (12) ◽  
pp. 938-946
Author(s):  
Xiaoxing Wang ◽  
Wenwen Du ◽  
Xianglin Zhang ◽  
Pengmei Li
Keyword(s):  
Clinical Practice ◽  
B Cell ◽  
Drug Exposure ◽  
Kidney Diseases ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Pharmacokinetic Data ◽  
B Cell Malignancies ◽  
Related Factors ◽  
Factors Affecting

Background: The anti-CD20 antibody rituximab, which promotes the selective depletion of CD20 positive B cells, was the first targeted therapy that was approved for the treatment of B-cell malignancies, and it is now widely prescribed in both malignant and non-malignant, immune-related diseases. However, the cause of its various clinical responses in certain diseases, have not been clearly elucidated. The variabilities in inter-individual pharmacokinetic and the emerging evidence of the relationships between pharmacokinetic and pharmacodynamic may provide a better understanding of this drug. Methods: We searched and summarized the latest published articles on rituximab pharmacokinetic profiles and the pharmacokinetic/pharmacodynamic models in different patient populations, including B-cell malignancies, rheumatoid arthritis, ANCA-associated vasculitis, and glomerular kidney diseases. Results: Most pharmacokinetic data are drawn from clinical studies in oncology clinical practice. Body weight, gender, and antigen-related factors are proven to be the key factors affecting rituximab pharmacokinetics. In addition, the positive exposure-response relations were reported, which provide encouraging evidence for individualized therapies. While in immune disorders, especially in the off-labeled indications, pharmacokinetic studies are quite limited. Compared with that in B-cell malignancies, the differences in the pharmacokinetic parameters may be attributed to the different pathogeneses of diseases, mechanisms of action and dosing strategies. However, the correlation between drug exposure and clinical outcomes remains unclear. Conclusion: Here, we provide an overview of the complexities associated with rituximab pharmacokinetics and pharmacodynamics in different diseases. Although many influencing factors need to be verified in future studies, a better understanding of the relationships between pharmacokinetic and pharmacodynamic may assist in optimizing rituximab clinical practice.

Dissemination and Implementation of Evidence-Based Assessment

2018 ◽  
pp. 17-31
Author(s):  
Amanda Jensen-Doss ◽  
Lucia M. Walsh ◽  
Vanesa Mora Ringle
Keyword(s):  
Public Health ◽  
Clinical Practice ◽  
Therapeutic Relationship ◽  
Clinical Assessment ◽  
Routine Clinical Practice ◽  
Dissemination And Implementation ◽  
Clinical Settings ◽  
Assessment Practices ◽  
Evidence Based ◽  
Case Formulation

Abstract: The goal of evidence-based practice in psychology (EBPP) is to improve public health through the application of research-supported assessment, case formulation, therapeutic relationship, and treatment approaches. Although EBPP is defined broadly, many efforts to improve practice have focused on treatment, with less attention paid to other aspects of practice. In this chapter, it is argued that significant work is needed to encourage the dissemination of information about evidence-based assessment (EBA) and its implementation in routine clinical practice. The chapter discusses how EBA differs from usual clinical assessment practices and describes efforts to increase the use of EBA. Finally, the chapter presents suggestions for steps that must be taken to advance the use of EBA in clinical settings.

scholarly journals Modest but Variable Effect of Rifampin on Steady-State Plasma Pharmacokinetics of Efavirenz in Healthy African-American and Caucasian Volunteers

2011 ◽  
Vol 55 (7) ◽  
pp. 3527-3533 ◽  
Author(s):  
Awewura Kwara ◽  
Karen T. Tashima ◽  
Julie B. Dumond ◽  
Pamela Poethke ◽  
Jaclyn Kurpewski ◽  
...  
Keyword(s):  
Body Weight ◽  
High Performance ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Time Curve ◽  
Variable Effect ◽  
Coefficients Of Variation ◽  
Tuberculosis Therapy

ABSTRACTEfavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to receive 600 mg efavirenz/day or 600 mg efavirenz with 600 mg rifampin/day for 8 days, with plasma samples collected for pharmacokinetic analysis over 24 h on day 8. Treatments were then crossed over after at least a 2-week washout period, and procedures were repeated. Efavirenz concentrations were determined by high-performance liquid chromatography (HPLC), and pharmacokinetic parameters were estimated by noncompartmental analysis. Efavirenz pharmacokinetic differences between treatment periods were evaluated by pairedttest. The coefficients of variation in efavirenz plasma AUC0-24(area under the concentration-time curve from 0 to 24 h) were 50% and 56% in the absence and presence of rifampin, respectively. Of the 11 evaluable subjects (6 white, 5 black; 6 women, 5 men), the geometric mean AUC0-24ratio on/off rifampin (90% confidence interval) was 0.82 (0.72, 0.92), with individual AUC0-24ratios varying from 0.55 to 1.18. Five subjects had a 24-hour efavirenz concentration (C24) of <1,000 ng/ml on rifampin. They were more likely to have received a lower dose in milligrams/kilogram of body weight and to have lower efavirenz AUC0-24values in the basal state. Although rifampin resulted in a modest reduction in efavirenz plasma exposure in subjects as a whole, there was high variability in responses between subjects, suggesting that efavirenz dose adjustment with rifampin may need to be individualized. Body weight and genetic factors will be important covariates in dosing algorithms.

Factors Affecting the Pharmacokinetic Characteristics of Rapacuronium 

1999 ◽  
Vol 90 (4) ◽  
pp. 993-1000 ◽  
Author(s):  
Dennis M. Fisher ◽  
Raymond Kahwaji ◽  
David Bevan ◽  
George Bikhazi ◽  
Robert J. Fragen ◽  
...  
Keyword(s):  
Plasma Clearance ◽  
Bolus Dose ◽  
Plasma Concentrations ◽  
Rapid Onset ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Single Bolus ◽  
Age Related ◽  
Single Bolus Dose

Background Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics. Methods Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters. Results Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration. Conclusions In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

scholarly journals Turnaround Time for Microbiological Testing of Tuberculosis in Routine Clinical Practice and Time to Patient Initiation on Treatment, Iganga Hospital, Uganda: 2012-2017

2021 ◽  
Author(s):  
Angella Musewa ◽  
Lilian Bulage ◽  
Joseph Frank Maganda ◽  
Alex Riolexus Ario
Keyword(s):  
Clinical Practice ◽  
Treatment Initiation ◽  
Turnaround Time ◽  
Drug Susceptibility Testing ◽  
Routine Clinical Practice ◽  
Smear Microscopy ◽  
Reference Laboratory ◽  
Time To Initiation ◽  
Mdr Tb ◽  
Microbiological Testing

Abstract Background: Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (Mtb) that is resistant to atleast isoniazid and rifampicin. Delayed diagnosis and treatment initiation lead to increased transmission and poor clinical outcomes. Although GeneXpert MTB/RIF detects Mtb and rifampicin resistance within 2 hours, the TB control program needs to understand the turnaround time (TAT) from specimen collection to treatment initiation and its impact on treatment outcomes for patients with Rif-resistant TB in Uganda. We quantified the TAT overall and at each step of the process for diagnosis of Rif-resistant TB in routine clinical practice and time to initiation on appropriate treatment over a 5-year period.Methods: We conducted a retrospective study in Iganga General Hospital, Eastern Uganda. Both Rif-resistant and MDR TB cases are recorded in the same register. We abstracted data from the MDR-TB clinic and laboratory registers (Form 2A and 096B) at Iganga Hospital, 2012-2017, including dates for smear microscopy, Xpert MTB/RIF, initiating MDR-TB patients on treatment after the Xpert MTB/RIF test, and dates for Drug Susceptibility Testing (DST). We performed descriptive and survival analysis to estimate the TAT for microbiological testing and time to initiation on treatment among MDR-TB patients.Results: Overall, we analyzed sixty-three (63) records, including specimens from Iganga Hospital patients and referrals from other health facilities. Of 63 records, 81% (51/63) had microscopy results, 97% (61/63) had Xpert MTB/RIF results, and 98% (62/63) had DST results. The median TAT for smear microscopy was the same day or within 1 day for 38/51 (75%) of the patients, ranging from 2-31 days for the rest. TAT for Xpert MTB/RIF results was the same day or within 1 day for 45/61 (75%), while the rest ranged from 2-183 days. Treatment initiation was within 28 days for 30/61 (50%). Reporting results for DST, took a median time of 13 days (IQR: 10-40 days) with an overall range of 0-334 days. Conclusion: Prompt Xpert MTB/RIF testing and result reporting allows timely treatment initiation. We recommend timely release of DST results by the National Tuberculosis Reference Laboratory or decentralization of DST services so as to mitigate delays and improve patient re-evaluation.

scholarly journals The Statistical Analysis of Pharmacokinetic Parameters in the Context of Bioequivalence Testing of Two Anthelmintic Formulas Based on Ivermectine and Triclabendazole in Sheep

2019 ◽  
Vol 65 (2) ◽  
pp. 60-65
Author(s):  
Lenard Farczadi ◽  
Laurian Vlase ◽  
Orsolya Melles ◽  
Ramona Tolomeiu ◽  
Octavia Tamas-Krumpe ◽  
...  
Keyword(s):  
High Performance ◽  
Reference Product ◽  
Plasma Concentrations ◽  
Pharmaceutical Formulations ◽  
Relative Bioavailability ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Test Product

AbstractConducting bioequivalence studies is an essential step during the market authorization process of generic pharmaceutical formulations, for both human or veterinary use. The aim of the present study was to evaluate the pharmacokinetics of triclabendazole sulphoxide, the main metabolite of triclabendazole, and ivermectin in order to evaluate the bioavailability and bioequivalence of a novel sheep anthelmintic formulation of oral suspension for sheep treatment containing triclabendazole 50 mg/mL and ivermectin 1 mg/mL compared to the reference product. In order to determine relative bioavailability of the test product with respect to the reference product the study was conducted on 36 clinically healthy sheep, following an unicentric, randomized, cross-over, two-sequence, two-treatment and 14-day wash-out study design. For the determination of triclabendazole sulphoxide and ivermectin sheep plasma concentrations, two rapid, selective high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) methods were developed and validated. The measured plasma concentrations of triclabendazole sulphoxide and ivermectin were used for the pharmacokinetic analysis and the determination of bioequivalence between the test product with regards to the reference product. The noncompartmental analysis of the pharmacokinetic data for both triclabendazole sulphoxide and ivermectin showed similarities between first-order kinetics of the test and reference product. The relevant pharmacokinetic parameters (Cmax, AUClast, AUCtot) were determined and the bioequivalence between the test and reference product could be concluded.

scholarly journals A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges

2020 ◽  
Vol 65 (1) ◽  
pp. e01998-20
Author(s):  
Nilesh Kumta ◽  
Jason A. Roberts ◽  
Jeffrey Lipman ◽  
Wai Tat Wong ◽  
Gavin M. Joynt ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Pharmacokinetic Data ◽  
Significant Heterogeneity ◽  
Related Factors ◽  
Meningeal Inflammation

ABSTRACTVentriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically appraise studies with reported antibiotic concentrations or pharmacokinetic data in cerebrospinal fluid of critically ill patients without meningeal inflammation. We systematically reviewed the literature to identify published reports and studies describing antibiotic concentrations, pharmacokinetics, and pharmacokinetics/pharmacodynamics in cerebrospinal fluid of critically ill patients with uninflamed meninges. Fifty-eight articles met the inclusion criteria. There was significant heterogeneity in methodologies and results. When available, antibiotic pharmacokinetic parameters displayed large intersubject variability. Intraventricular dosing achieved substantially higher antibiotic concentrations in cerebrospinal fluid than did intravenous doses. Few studies conducted a robust pharmacokinetic analysis and described relevant clinical pharmacokinetic/pharmacodynamic indices and exposure targets in cerebrospinal fluid. Robust and clinically relevant antibiotic pharmacokinetic data describing antibiotic disposition in cerebrospinal fluid are necessary. Such studies should use a standardized approach to accurately describe pharmacokinetic variability. These data should ideally be tied to clinical outcomes whereby therapeutic targets in the cerebrospinal fluid can be better defined. Altered dosing strategies, in conjunction with exploring the utility of therapeutic drug monitoring, can then be developed to optimize antibiotic exposure with the goal of improving outcomes in this difficult-to-treat patient group.

scholarly journals Levofloxacin Population Pharmacokinetics in South African Children Treated for Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Paolo Denti ◽  
Anthony J. Garcia-Prats ◽  
Heather R. Draper ◽  
Lubbe Wiesner ◽  
Jana Winckler ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Older Children ◽  
Dose Selection ◽  
Mixed Effects Modeling ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Similar Dose ◽  
Mdr Tb

ABSTRACT Levofloxacin is increasingly used in the treatment of multidrug-resistant tuberculosis (MDR-TB). There are limited pediatric pharmacokinetic data to inform dose selection for children. Children routinely receiving levofloxacin (250-mg adult tablets) for MDR-TB prophylaxis or disease in Cape Town, South Africa, underwent pharmacokinetic sampling following receipt of a dose of 15 or 20 mg/kg of body weight given as a whole or crushed tablet(s) orally or via a nasogastric tube. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. Model-based simulations were performed to estimate the doses across weight bands that would achieve adult exposures with 750-mg once-daily dosing. One hundred nine children were included. The median age was 2.1 years (range, 0.3 to 8.7 years), and the median weight was 12 kg (range, 6 to 22 kg). Levofloxacin followed 2-compartment kinetics with first-order elimination and absorption with a lag time. After inclusion of allometric scaling, the model characterized the age-driven maturation of clearance (CL), with the effect reaching 50% of that at maturity at about 2 months after birth and 100% of that at maturity by 2 years of age. CL in a typical child (weight, 12 kg; age, 2 years) was 4.7 liters/h. HIV infection reduced CL by 16%. By use of the adult 250-mg formulation, levofloxacin exposures were substantially lower than those reported in adults receiving a similar dose on a milligram-per-kilogram basis. To achieve adult-equivalent exposures at a 750-mg daily dose, higher levofloxacin pediatric doses of from 18 mg/kg/day for younger children with weights of 3 to 4 kg (due to immature clearance) to 40 mg/kg/day for older children may be required. The doses of levofloxacin currently recommended for the treatment of MDR-TB in children result in exposures considerably lower than those in adults. The effects of different formulations and formulation manipulation require further investigation. We recommend age- and weight-banded doses of 250-mg tablets of the adult formulation most likely to achieve target concentrations for prospective evaluation.

Structured Data Entry for Reliable Acquisition of Pharmacokinetic Data

1996 ◽  
Vol 35 (03) ◽  
pp. 261-264 ◽  
Author(s):  
T. Schromm ◽  
T. Frankewitsch ◽  
M. Giehl ◽  
F. Keller ◽  
D. Zellner
Keyword(s):  
Text Processing ◽  
Data Entry ◽  
Processing System ◽  
Database System ◽  
Structured Data ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Probability Of Error ◽  
Error Frequency ◽  
Estimated Error

Abstract:A pharmacokinetic database was constructed that is as free of errors as possible. Pharmacokinetic parameters were derived from the literature using a text-processing system and a database system. A random data sample from each system was compared with the original literature. The estimated error frequencies using statistical methods differed significantly between the two systems. The estimated error frequency in the text-processing system was 7.2%, that in the database system 2.7%. Compared with the original values in the literature, the estimated probability of error for identical pharmacokinetic parameters recorded in both systems is 2.4% and is not significantly different from the error frequency in the database. Parallel data entry with a text-processing system and a database system is, therefore, not significantly better than structured data entry for reducing the error frequency.

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