scholarly journals 1326. Vancomycin Area Under the Concentration-Time Curve (AUC) Estimation Using a Bayesian Approach Versus First-Order Pharmacokinetic Equations: A Pilot Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S673-S673
Author(s):  
Jeffrey Pearson ◽  
Yazed S Alsowaida ◽  
B S Pharm ◽  
David W Kubiak ◽  
Mary P Kovacevic ◽  
...  
Keyword(s):  
Pilot Study ◽  
Median Time ◽  
Bayesian Modeling ◽  
Surgical Prophylaxis ◽  
Time Curve ◽  
Team Members ◽  
First Order ◽  
Concentration Time ◽  
Study Team ◽  
Auc Estimation

Abstract Background Current guidelines endorse area under the concentration-time curve (AUC)-based monitoring over trough-only monitoring for systemic vancomycin. Vancomycin AUC can be estimated using either Bayesian modeling software or first-order pharmacokinetic (PK) calculations. The objective of this pilot study was to evaluate and compare the efficiency and feasibility of these two approaches for calculating the estimated vancomycin AUC. Methods A single-center crossover study was conducted in four medical/surgical units at Brigham and Women’s Hospital over a 3-month time period. All adult patients who received vancomycin were included. Patients were excluded if they were receiving vancomycin for surgical prophylaxis, were on hemodialysis, if vancomycin was being dosed by level, or if vancomycin levels were never drawn. The primary endpoint was the amount of time study team members spent calculating the estimated AUC and determining regimen adjustments with Bayesian modeling compared to first-order PK calculations. Secondary endpoints included the number of vancomycin levels drawn and the percent of those drawn that were usable for AUC calculations. Results One hundred twenty-four patients received vancomycin during the study, of whom 47 met inclusion criteria. The most likely reasons for exclusion were receiving vancomycin for surgical prophylaxis (n=40) or never having vancomycin levels drawn (n=32). The median time taken to assess levels in the Bayesian arm was 9.3 minutes [interquartile range (IQR) 7.8-12.4] versus 6.8 minutes (IQR 4.8-8.0) in the 2-level PK arm (p=0.004). However, if Bayesian software is integrated into the electronic health record (EHR), the median time to assess levels was 3.8 minutes (IQR 2.3-6.8, p=0.019). In the Bayesian arm, 30 of 34 vancomycin levels (88.2%) were usable for AUC calculations, compared to 28 of 58 (48.3%) in the 2-level PK arm. Conclusion With EHR integration, the use of Bayesian software to calculate the AUC was more efficient than first-order PK calculations. Additionally, vancomycin levels were more likely to be usable in the Bayesian arm, thereby avoiding delays in estimating the vancomycin AUC. Disclosures All Authors: No reported disclosures

scholarly journals Pharmacokinetics of Ethambutol under Fasting Conditions, with Food, and with Antacids

1999 ◽  
Vol 43 (3) ◽  
pp. 568-572 ◽  
Author(s):  
Charles A. Peloquin ◽  
Amy E. Bulpitt ◽  
George S. Jaresko ◽  
Roger W. Jelliffe ◽  
James M. Childs ◽  
...  
Keyword(s):  
Maximum Concentration ◽  
Pharmacokinetic Model ◽  
Mass Spectrometry Data ◽  
Gas Chromatography Mass Spectrometry ◽  
High Fat ◽  
Time Curve ◽  
First Order ◽  
Concentration Time ◽  
Males And Females ◽  
Fat Meal

ABSTRACT Ethambutol (EMB) is the most frequent “fourth drug” used for the empiric treatment of Mycobacterium tuberculosis and a frequently used drug for infections caused by Mycobacterium avium complex. The pharmacokinetics of EMB in serum were studied with 14 healthy males and females in a randomized, four-period crossover study. Subjects ingested single doses of EMB of 25 mg/kg of body weight under fasting conditions twice, with a high-fat meal, and with aluminum-magnesium antacid. Serum was collected for 48 h and assayed by gas chromatography-mass spectrometry. Data were analyzed by noncompartmental methods and by a two-compartment pharmacokinetic model with zero-order absorption and first-order elimination. Both fasting conditions produced similar results: a mean (± standard deviation) EMB maximum concentration of drug in serum (C max) of 4.5 ± 1.0 μg/ml, time to maximum concentration of drug in serum (T max) of 2.5 ± 0.9 h, and area under the concentration-time curve from 0 h to infinity (AUC0–∞) of 28.9 ± 4.7 μg · h/ml. In the presence of antacids, subjects had a mean C maxof 3.3 ± 0.5 μg/ml, T max of 2.9 ± 1.2 h, and AUC0–∞ of 27.5 ± 5.9 μg · h/ml. In the presence of the Food and Drug Administration high-fat meal, subjects had a mean C max of 3.8 ± 0.8 μg/ml, T max of 3.2 ± 1.3 h, and AUC0–∞ of 29.6 ± 4.7 μg · h/ml. These reductions in C max, delays inT max, and modest reductions in AUC0–∞ can be avoided by giving EMB on an empty stomach whenever possible.

Co-administration of Dalbergia odorifera Increased Bioavailability of Salvia miltiorrhizae in Rabbits

2007 ◽  
Vol 35 (05) ◽  
pp. 831-840 ◽  
Author(s):  
Xiaohui Zheng ◽  
Xinfeng Zhao ◽  
Shixiang Wang ◽  
Kai Luo ◽  
Yinmao Wei ◽  
...  
Keyword(s):  
High Performance ◽  
Salvia Miltiorrhiza ◽  
Blood Stasis ◽  
Time Curve ◽  
Healthy Group ◽  
First Order ◽  
Concentration Time ◽  
Salvia Miltiorrhizae ◽  
Dalbergia Odorifera ◽  
Compartment Open Model

This study was to investigate the effect of Dalbergia odorifera (DO) on the pharmacokinetics of Danshensu in Salvia miltiorrhiza (SM) in healthy rabbits and rabbits with qi-stagnancy and blood stasis. Thirty two healthy rabbits were involved in the whole experiment. Qi-stagnancy and blood stasis rabbits were obtained by treating the limbs of 16 adnephrin rabbits in an ice-bath for 6.0 min. The rest of rabbits were equally divided into 2 healthy groups. One healthy group and 8 qi-stagnancy and blood stasis rabbits were orally administrated with SM (5.0 g/kg), and the other 8 healthy rabbits and 8 qi-stagnancy and blood stasis rabbits with SM (5.0 g/kg) coupled with DO (2.5 g/kg). The plasma (Danshensu) concentration–time curve was measured by high performance liquid chromatography (HPLC)-electrospray ionization (ESI)-trap mass (MS-MS). Danshensu in plasma was confirmed to be two-compartment open model with a first order absorption phase in all groups. Moreover, the area under curve (0-∞) of Danshensu was significantly increased both in healthy group and in qi-stagnancy and blood stasis group after administration of SM coupled with DO. This result was in accordance with the “Jun-Shi pairing herbs theory” of traditional Chinese medicine (TCM).

scholarly journals Determination of Appropriate Weight-Based Cutoffs for Empiric Cefazolin Dosing Using Data from a Phase 1 Pharmacokinetics and Safety Study of Cefazolin Administered for Surgical Prophylaxis in Pediatric Patients Aged 10 to 12 Years

2015 ◽  
Vol 59 (7) ◽  
pp. 4173-4180 ◽  
Author(s):  
Michael L. Schmitz ◽  
Jeffrey L. Blumer ◽  
Wes Cetnarowski ◽  
Christopher M. Rubino
Keyword(s):  
Pediatric Patients ◽  
Phase 1 ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Time Data ◽  
Surgical Prophylaxis ◽  
Open Label ◽  
Time Curve ◽  
Concentration Time ◽  
Few Data

ABSTRACTDespite over 40 years of worldwide usage, relatively few data have been published on the pharmacokinetics of cefazolin in pediatric surgical patients. The primary objectives of this study were to examine the pharmacokinetics and safety of cefazolin in children 10 to 12 years of age (inclusive) receiving 1 or 2 g of cefazolin, based on body weight. This multiple-center, open-label study enrolled pediatric patients electively scheduled for surgical procedures who required cefazolin as part of their routine clinical management. Patients weighing ≥25 to <50 kg received a 1-g dose, and patients weighing ≥50 to ≤85 kg received a 2-g dose. Postdose pharmacokinetic and safety assessments were conducted following drug administration. Cefazolin concentration-time data were analyzed by using both noncompartmental and population pharmacokinetics methods. Monte Carlo simulations were performed to identify appropriate weight-based cutoffs for the dosing of children aged 10 to 17 years of age. Twelve patients were enrolled in this study and provided the requisite pharmacokinetic data. In general, cefazolin was well tolerated. The mean cefazolin terminal elimination half-life, clearance, and area under the concentration-time curve from time zero to infinity in this population were 1.95 h, 0.804 ml/min/kg, and 607 mg · h/liter, respectively. Patients weighing 50 to 60 kg exhibited elevated cefazolin exposures. Observed pharmacokinetic parameters and simulation results indicated that a weight-based cutoff of 60 kg is predicted to provide cefazolin exposure consistent with that observed in normal, healthy adults at recommended doses for surgical prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01904357.)

scholarly journals Perceptions of Adolescents With Cancer Related to a Pain Management App and Its Evaluation: Qualitative Study Nested Within a Multicenter Pilot Feasibility Study (Preprint)

2017 ◽  
Author(s):  
Lindsay A Jibb ◽  
Bonnie J Stevens ◽  
Paul C Nathan ◽  
Emily Seto ◽  
Joseph A Cafazzo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pain Management ◽  
Pilot Study ◽  
Qualitative Study ◽  
Study Protocol ◽  
Consensus Conference ◽  
Management Support ◽  
Team Members ◽  
Study Team ◽  
Related Quality

BACKGROUND Pain in adolescents with cancer is common and negatively impacts health-related quality of life. The Pain Squad+ smartphone app, capable of providing adolescents with real-time pain management support, was developed to enhance pain management using a phased approach (ie, systematic review, consensus conference and vetting, iterative usability testing cycles). A 28-day Pain Squad+ pilot was conducted with 40 adolescents with cancer to evaluate the feasibility of implementing the app in a future clinical trial and to obtain estimates of treatment effect. OBJECTIVE The objective of our nested qualitative study was to elucidate the perceptions of adolescents with cancer to determine the acceptability and perceived helpfulness of Pain Squad+, suggestions for app improvement, and satisfaction with the pilot study protocol. METHODS Post pilot study participation, telephone-based, semistructured, and audio-recorded exit interviews were conducted with 20 adolescents with cancer (12-18 years). All interviews were transcribed and independently coded by 2 study team members. Content analysis was conducted to identify data categories and overarching themes. RESULTS Five major themes comprising multiple categories and codes emerged. These themes focused on the acceptability of the intervention, acceptability of the study, the perceived active ingredients of the intervention, the suitability of the intervention to adolescents’ lives, and recommendations for intervention improvement. CONCLUSIONS Overall, Pain Squad+ and the pilot study protocol were acceptable to adolescents with cancer. Suggestions for intervention and study improvements will be incorporated into the design of a future randomized clinical trial (RCT) aimed at assessing the effectiveness of Pain Squad+ on adolescents with cancer health outcomes.

scholarly journals Rational dosing of HCQ for COVID-19_pre-print

2020 ◽  
Author(s):  
Kevin Downes ◽  
Kathleen Chiotos ◽  
Julie Fitzgerald ◽  
Marc H Scheetz ◽  
Athena F. Zuppa
Keyword(s):  
Plasma Concentrations ◽  
Safety Data ◽  
Loading Dose ◽  
Maximal Concentration ◽  
In Vitro Activity ◽  
Time Curve ◽  
First Order ◽  
Concentration Time ◽  
Autoimmune Conditions

Background: Hydroxychloroquine (HCQ) has in vitro activity against SARS-CoV-2. However, datato inform optimal human dosing are limited.Methods: We conducted Monte Carlo simulations of HCQ sulfate using a published populationpharmacokinetic model. The model informing our simulations described a 2-compartmentlinear model with first-order absorption with a lag, derived from plasma HCQ concentrationdata from 22 healthy adults and 69 patients with malaria. Using the final PK model, we performed 1000 simulations for the plasma concentrations of HCQ sulfate based on various approved dosages (i.e. acute malaria, autoimmune conditions) and proposed dosing regimensfor treatment of COVID-19. The results of simulations were used to derive the area under the concentration-time curve (AUC), maximal concentration, and time to maximal concentration for each evaluated regimen.Results: The use of a loading dose, as with acute malaria dosing, resulted in rapid achievementof maximal concentrations early in the treatment course, which were maintained with dailydosing thereafter. The use of once or twice daily doses without a loading dose led to slowlyincreasing plasma concentrations through day 10. Simulated regimens that employed an 800mg loading dose for adults (13 mg/kg for children) followed by 400 mg at 6 or 12 hours (6.5mg/kg for children) achieved the greatest AUC0-24.Conclusions: Based on our findings, along with established safety data from malarial studies,we believe that approved dosing for treatment acute malaria is the most reasonable and safestapproach if HCQ will be used to treat COVID-19.

A Comparative Pharmacokinetic Profile of Trahydropalmatine After Oral Administration of its Monomer, Rhizoma Corydalis Alkaloid Extracts and Tong-Bi-Si-Wei-Fang to Rats

2019 ◽  
Vol 15 (4) ◽  
pp. 338-345
Author(s):  
Lijun Ni ◽  
Lu Ding ◽  
Liguo Zhang ◽  
Shaorong Luan
Keyword(s):  
Oral Administration ◽  
Panax Notoginseng ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Bone Diseases ◽  
Glycyrrhiza Uralensis ◽  
Pharmacokinetic Property ◽  
Time Curve ◽  
Concentration Time

Background: Tong-Bi-Si-Wei-Fang (TBSWF) is a candidate formula of Traditional Chinese Medicine (TCM) for treating rheumatoid bone diseases, which is composed of rhizoma corydalis alkaloids, saponins of glycyrrhiza uralensis and panax notoginseng, flavonoids of rhizoma drynariae and glycyrrhiza uralensis. </P><P> Objective: Trahydropalmatine (THP), the main active ingredient of rhizoma corydalis alkaloids, was selected to study in vivo pharmacokinetics and druggability of TBSWF. Methods: The plasma concentration-time (C-T) profiles of THP and the pharmacokinetic property parameters after oral administration of THP monomer, extract of corydalis alkaloids (ECA) and TBSWF to rats, respectively were compared by a fully-validated HPLC method. Results: Compared to the THP monomer, the THP in TBSWF is absorbed faster, resides in the plasma longer and has a similar apparent volume of distribution Vz/F (10~20 L/kg). Compared to THP monomer and THP in TBSWF, the area under the concentration-time curve AUC 0-t of THP in ECA decreases two-third; Vz/F of THP in ECA (85.02 L/kg) is significantly higher than that of THP in TBSWF(p <0.05). Unlike THP monomer and THP in ECA, double peaks are observed in the C-T profile of THP after oral administration of TBSWF. THP in TBSWF exhibits slow release to a certain degree. Conclusion: The interactions among the ingredients of TBSWF promote the adsorption and prolong the residence time of THP in vivo, and provide an explanation for the advantages of TBSWF from the point of pharmacokinetics.

Prescription in Locker Box (PILBOX): Remodeling of the Medication Collection Process (Preprint)

2020 ◽  
Author(s):  
Lim Jit Fan Christina ◽  
Goh Boon Kwang ◽  
Chee Wing Ling Vivian ◽  
Tang Woh Peng ◽  
Goh Qiuling Bandy
Keyword(s):  
Cross Sectional Study ◽  
Ease Of Use ◽  
Prescription Medications ◽  
Pharmacy Staff ◽  
Cross Sectional ◽  
Team Members ◽  
Face To Face ◽  
Ranking Score ◽  
Study Team ◽  
Willingness To Use

BACKGROUND Traditionally, patients wishing to obtain their prescription medications have had to present themselves physically at pharmacy counters and collect their medications via face-to-face interactions with pharmacy staff. Prescription in Locker Box (PILBOX) is a new innovation which allows patients and their caregivers to collect their medication asynchronously, 24/7 at their convenience, from medication lockers instead of from pharmacy staff and at any time convenient to them instead of being restricted to pharmacy operating hours. OBJECTIVE This study aimed to determine the willingness by patients/caregivers to use this new innovation and factors that affect their willingness. METHODS This prospective cross-sectional study was conducted over 2 months at 2 public primary healthcare centres in Singapore. Patients or caregivers who were at least 21 yo and turned up at the pharmacies to collect medications were administered a self-developed 3-part questionnaire face-to-face by trained study team members, if they gave their consent to participate in the study. RESULTS A total of 222 participants completed the study. About 40% of them participants were willing to use the PILBOX to collect their medications. Amongst the participants who were keen to use the PILBOX service, slightly more than half (i.e. 52.8%) of them were willing to pay for the PILBOX service. The participants felt that the ease of use (3.46±1.21 i.e. mean of ranking score ± standard deviation) of the PILBOX was the most important factor that would affect their willingness to use the medication pick up service. This was followed by “waiting time” (3.37±1.33), cost of using the medication pick up service (2.96±1.44) and 24/7 accessibility (2.62±1.35). This study also found that age (p=0.006), language literacy (p=0.000), education level (p=0.000), working status (p=0.011) and personal monthly income (p=0.009) were factors that affected the willingness of the patients or caregivers to use the PILBOX. CONCLUSIONS Patients and caregivers are keen to use PILBOX to collect their medications for its convenience and the opportunity to save time, if it is easy to use and not costly.

scholarly journals Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1598
Author(s):  
Tung-Hu Tsai ◽  
Yu-Jen Chen ◽  
Li-Ying Wang ◽  
Chen-Hsi Hsieh
Keyword(s):  
Radiation Therapy ◽  
Rat Model ◽  
Systemic Therapy ◽  
Stereotactic Body Radiation Therapy ◽  
Time Curve ◽  
Stereotactic Body Radiation ◽  
Concentration Time ◽  
Sequential Regimen ◽  
Freely Moving

Concurrent and sequential regimens involving radiotherapy (RT) and lenvatinib were designed with off-target or stereotactic body radiation therapy (SBRT) doses in a freely moving rat model to evaluate the effect of RT on the pharmacokinetics (PK) of lenvatinib. Liver RT concurrent with lenvatinib decreased the area under the concentration–time curve of lenvatinib concentration (AUClenvatinib) by 51.1% with three fractions of 2 Gy (RT2Gy×3f’x, p = 0.03), and 48.9% with RT9Gy×3f’x (p = 0.03). The AUClenvatinib increased by 148.8% (p = 0.008) with RT2Gy×3f’x, and 68.9% (p = 0.009) with RT9Gy×3f’x in the sequential regimen compared to the concurrent regimen. There were no differences in the AUClenvatinib between RT2Gy×3f’x and RT9Gy×3f’x in the concurrent or sequential regimen. Both the RT2Gy×3f’x and RT9Gy×3f’x concurrent regimens markedly decreased the biodistribution of lenvatinib in the heart, liver, lung, spleen, and kidneys, which ranged from 31% to 100% for RT2Gy×3f’x, and 11% to 100% for RT9Gy×3f’x, compared to the sham regimen. The PK and biodistribution of lenvatinib can be modulated by simultaneous off-target irradiation and SBRT doses. The timing of lenvatinib administration with respect to RT, impacted the PK and biodistribution of the drug. Additionally, off-target and SBRT doses had a similar ability to modulate the effect of systemic therapy.

Effectiveness of a vancomycin dosing protocol guided by area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) with multidisciplinary team support to improve hospital-wide adherence to a vancomycin dosing protocol: A pilot study

2021 ◽  
pp. 1-6
Author(s):  
Panipak Katawethiwong ◽  
Anucha Apisarnthanarak ◽  
Kittiya Jantarathaneewat ◽  
David J. Weber ◽  
David K. Warren ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Multidisciplinary Team ◽  
Kidney Injury ◽  
University Hospital ◽  
Routine Practice ◽  
Post Intervention ◽  
Coagulase Negative Staphylococci ◽  
Time Curve ◽  
Concentration Time ◽  
Quasi Experimental

Abstract Background: Limited data are available on the implementation of an area under the concentration-time curve (AUC)–based dosing protocol with multidisciplinary team (MT) support to improve adherence with vancomycin dosing protocol. Objective: To evaluate the effectiveness of an AUC-based dosing protocol with MT support intervention with adherence to a hospital-wide vancomycin dosing protocol at Thammasat University Hospital. Method: We conducted a quasi-experimental study in patients who were prescribed intravenous vancomycin. The study was divided into 2 periods; (1) the preintervention period when the vancomycin dosing protocol was already applied in routine practice and (2) the post-intervention period when the implementation of an AUC-based dosing protocol with MT support was added to the existing vancomycin dosing protocol. The primary outcome was the rate of adherence, and the secondary outcomes included acute kidney injury events, vancomycin-related adverse events, and 30-day mortality rate. Results: In total, 240 patients were enrolled. The most common infections were skin and soft-tissue infections (24.6%) and bacteremia (24.6%). The most common pathogens were coagulase-negative staphylococci (19.6%) and Enterococcus spp (15.4%). Adherence with the vancomycin dosing protocol was significantly higher in the postintervention period (90.8% vs 55%; P ≤ .001). By multivariate analysis, an AUC-based dosing protocol with MT support was the sole predictor for adherence with the vancomycin dosing protocol (adjusted odds ratio, 10.31; 95% confidence interval, 4.54–23.45; P ≤ .001). The 30-day mortality rate was significantly lower during the postintervention period (8.3% vs 20%; P = .015). Conclusions: AUC-based dosing protocol with MT support significantly improved adherence with vancomycin dosing protocol and was associated with a lower 30-day mortality rate.

scholarly journals Evidence for Establishing the Clinical Breakpoint of Cefquinome against Haemophilus Parasuis in China

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 105
Author(s):  
Kun Mi ◽  
Da Sun ◽  
Mei Li ◽  
Haihong Hao ◽  
Kaixiang Zhou ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Antibacterial Activity ◽  
Inhibitory Concentration ◽  
High Morbidity ◽  
Haemophilus Parasuis ◽  
Wild Type ◽  
Time Curve ◽  
Resistance Change ◽  
Concentration Time ◽  
Clinical Experiments

Haemophilus parasuis can cause high morbidity and mortality in swine. Cefquinome possesses excellent antibacterial activity against pathogens causing diseases of the respiratory tract. This study aimed to establish the clinical breakpoint (CBP) of cefquinome against H. parasuis and to monitor the resistance change. Referring to the minimum inhibitory concentration (MIC) distribution of cefquinome against 131 H. parasuis isolates, the MIC50 and MIC90 were determined to be 0.125 and 1 μg/mL, respectively. And the epidemiological cutoff (ECOFF) value was 1 μg/mL. HPS42 was selected as a representative strain for the pharmacodynamic (PD) experiment, pharmacokinetic (PK) experiment and clinical experiments. The PK/PD index values, area under concentration-time curve (AUC)/MIC, of the bacteriostatic, bactericidal, and bacterial elimination effects were 23, 41, and 51 h, respectively. The PK/PD cutoff was calculated as 0.125 μg/mL by Monte Carlo simulation (MCS), and the clinical cutoff was 0.25−4 μg/mL by WindoW. Combing these three values, the CBP of cefquinome against H. parasuis was found to be 1 μg/mL. In conclusion, this was the first study to integrate various cutoffs to establish the CBP in the laboratory. It is helpful to distinguish wild type H. parasuis and reduce the probability of treatment failure.

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