Within-Patient Atazanavir Trough Concentration Monitoring in HIV-1-Infected Patients

2010 ◽  
Vol 24 (2) ◽  
pp. 216-222 ◽  
Author(s):  
Rustin D. Crutchley ◽  
Qing Ma ◽  
Adel Sulaiman ◽  
Jill Hochreitter ◽  
Gene D. Morse
Keyword(s):  
High Performance ◽  
Clinical Success ◽  
Primary Objective ◽  
Repeated Measurements ◽  
Therapeutic Drug ◽  
Target Values ◽  
Intrapatient Variability ◽  
Trough Concentrations ◽  
Hiv 1 ◽  
Interpatient Variation

Objective: Protease inhibitors (PIs) exhibit considerable interpatient pharmacokinetic variability in plasma trough concentrations. Therapeutic drug monitoring (TDM) is occasionally used to guide chronic dosing to achieve target trough concentrations, but its clinical success assumes minimal intrasubject variability. Therefore, our primary objective was to evaluate intrapatient variability in atazanavir (ATV) plasma trough concentrations in HIV-1-infected patients. Design/Methods: In a single-site, prospective, cohort study, patients on atazanavir with or without ritonavir (ATV/r or ATV) for 2 clinic visits were enrolled. Adherence and time since last dose (TSLD) were verified at each visit. ATV was assayed with high-performance liquid chromatography. Intra- and interpatient variation was evaluated using the median intraindividual percentage coefficient of variation (ICV). Results: The mean 24-hour ATV trough concentrations for the first and second visit for the ATV/r group (n = 10) was 598 (CV 84%) and 525 ng/mL (CV 66%), respectively ( P = .511), and 300 (CV 81%) and 434 ng/mL (CV 106%) for the ATV group (n = 4), respectively ( P = .369). Median ICV was 43.1% for all patients (range: 0.6%-107.6%), 38.1% (0.6%-107.6%) for the ATV/r group, and 33.1% (2.3%-87.6%) for the ATV group. Conclusions: Potential intrapatient variability in ATV troughs suggests that repeated measurements may be required to ensure that target values are maintained.

scholarly journals CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

2009 ◽  
Vol 53 (3) ◽  
pp. 863-868 ◽  
Author(s):  
Geetha Ramachandran ◽  
A. K. Hemanth Kumar ◽  
Sikhamani Rajasekaran ◽  
P. Kumar ◽  
K. Ramesh ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
High Performance ◽  
South India ◽  
Blood Levels ◽  
South Indian Population ◽  
South Indian ◽  
Immunodeficiency Virus ◽  
Trough Concentrations ◽  
Hiv 1

ABSTRACT The dose of efavirenz during concomitant rifampin (RMP) administration is a matter of debate. We studied the influence of RMP coadministration on the steady-state pharmacokinetics of efavirenz in human immunodeficiency virus type 1 (HIV-1)-infected patients in South India. Fifty-seven HIV-tuberculosis (TB)-coinfected and 15 HIV-1-infected patients receiving combination antiretroviral therapy (CART) with an efavirenz (600 mg once daily)-containing regimen were recruited. HIV-TB-coinfected patients were receiving treatment with RMP-containing regimens. A complete pharmacokinetic study was conducted with 19 HIV-TB patients on two occasions (with and without RMP). Trough concentrations of efavirenz were measured in the remaining 38 patients during RMP coadministration. The 15 HIV-infected patients underwent complete pharmacokinetic sampling on one occasion. Plasma efavirenz was estimated by high-performance liquid chromatography, and genotyping of CYP2B6 G516T polymorphism was performed by sequencing. Peak and trough concentrations and exposure to efavirenz were significantly higher in TT than in GT and GG genotype patients (P < 0.001). Although RMP coadministration decreased the peak and trough concentrations and exposure to efavirenz by 17.8, 20.4, and 18.6%, respectively, the differences were not statistically significant. The trough concentration of efavirenz was subtherapeutic (less than 1.0 μg/ml) in 6 (8%) of 72 patients. In this South Indian population of HIV-infected patients, CYP2B6 G516T polymorphism but not RMP coadministration significantly influenced the pharmacokinetics of efavirenz; patients with the TT genotype had very high blood levels of efavirenz. While a small proportion of patients had subtherapeutic efavirenz levels, the clinical implications are uncertain, as all had good immunological responses to CART.

scholarly journals CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Yilei Yang ◽  
Xin Huang ◽  
Yinping Shi ◽  
Rui Yang ◽  
Haiyan Shi ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Renal Transplant ◽  
High Performance ◽  
Therapeutic Drug ◽  
Transplant Patients ◽  
Cyp3a5 Genotype ◽  
Group I ◽  
Trough Concentrations ◽  
Renal Transplant Patients ◽  
Group Ii

Purpose: The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients.Method: All renal transplant patients were divided into CYP3A5*3/*3 homozygotes (group I) and CYP3A5*1 allele carriers (CYP3A5*1/*1 + CYP3A5*1/*3) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C0) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C0) (C0/D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C0/D.Results: In this study, a significant DDI between tacrolimus and nifedipine with respect to the CYP3A5*3 polymorphism was confirmed. In group I (n = 43), the C0/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); p = 0.002]. However, this difference was not detected in group II (n = 27) (p = 0.216). The co-administrated nifedipine and CYP3A5*3/*3 homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.Discussion: A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

scholarly journals Quantification of Teicoplanin Using the HPLC-UV Method for Clinical Applications in Critically Ill Patients in Korea

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 572
Author(s):  
Jaeok Lee ◽  
Eun-Kyoung Chung ◽  
Sung-Wook Kang ◽  
Hwa-Jeong Lee ◽  
Sandy-Jeong Rhie
Keyword(s):  
High Performance ◽  
Internal Standard ◽  
Polymyxin B ◽  
Therapeutic Drug ◽  
Ultraviolet Detector ◽  
Wide Range ◽  
External Standard ◽  
Analytical Accuracy ◽  
Trough Concentrations ◽  
Improved Accuracy

A high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method has been used to quantify teicoplanin concentrations in human plasma. However, the limited analytical accuracy of previously bioanalytical methods for teicoplanin has given rise to uncertainty due to the use of an external standard. In this study, an internal standard (IS), polymyxin B, was applied to devise a precise, accurate, and feasible HPLC-UV method. The deproteinized plasma sample containing teicoplanin and an IS of acetonitrile was chromatographed on a C18 column with an acidic mobile phase consisting of NaH2PO4 buffer and acetonitrile (78:22, v/v) by isocratic elution and detection at 220 nm. The linearity was in the range 7.8–500 mg/L calculated by the ratio of the teicoplanin signal to the IS signal. This analytical method, validated by FDA guidelines with ICH Q2 (R1), was successfully applied to analyze the plasma samples of patients in the intensive care unit for treating serious resistant bacterial infectious diseases, such as those by methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. The methods suggested the potential for use in routine clinical practice for therapeutic drug monitoring of teicoplanin, providing both improved accuracy and a wide range of linearity from lower than steady-state trough concentrations (10 mg/L) to much higher concentrations.

scholarly journals Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients

2019 ◽  
Vol 57 (8) ◽  
pp. 937-943 ◽  
Author(s):  
Vincent J Lempers ◽  
Edmé Meuwese ◽  
Annelies M Mavinkurve-Groothuis ◽  
Stefanie Henriet ◽  
Inge M van der Sluis ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Multiple Dose ◽  
Pediatric Patients ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Patient Demographics ◽  
Before And After ◽  
Intrapatient Variability ◽  
Trough Concentrations

Abstract Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients <19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin > 6 mg/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2–18.5) years, were identified in two centers. First Cmin (3.1 mg/l [0.1–13.5]) was obtained after 3 days (1–27) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16 mg/l (0.0 (undetectable)–28.0), with 24.1% of Cmin < 1 mg/l, 48.9% 1–4 mg/l, 9.3% 4–6 mg/l, and 17.7% > 6 mg/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin < 1 mg/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4 mg/l. Dose decreases at Cmin > 6 mg/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4 mg/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1–4 mg/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.

Personalized antibiotic therapy – a rapid high performance liquid chromatography–tandem mass spectrometry method for the quantitation of eight antibiotics and voriconazole for patients in the intensive care unit

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Tony Böhle ◽  
Ulrike Georgi ◽  
Dewi Fôn Hughes ◽  
Oliver Hauser ◽  
Gudrun Stamminger ◽  
...  
Keyword(s):  
Intensive Care ◽  
Antibiotic Therapy ◽  
High Performance ◽  
High Specificity ◽  
Serum Levels ◽  
Turnaround Time ◽  
Target Range ◽  
Therapeutic Drug ◽  
Monitoring Method ◽  
Adjustment Procedure

AbstractObjectivesFor a long time, the therapeutic drug monitoring of anti-infectives (ATDM) was recommended only to avoid the toxic side effects of overdosing. During the last decade, however, this attitude has undergone a significant change. Insufficient antibiotic therapy may promote the occurrence of drug resistance; therefore, the “one-dose-fits-all” principle can no longer be classified as up to date. Patients in intensive care units (ICU), in particular, can benefit from individualized antibiotic therapies.MethodsPresented here is a rapid and sufficient LC-MS/MS based assay for the analysis of eight antibiotics (ampicillin, cefepime, cefotaxime, ceftazidime, cefuroxime, linezolid, meropenem, and piperacillin) applicated by continuous infusion and voriconazole. In addition a dose adjustment procedure for individualized antibiotic therapy has been established.ResultsThe suggested dose adjustments following the initial dosing of 121 patient samples from ICUs, were evaluated over a period of three months. Only a minor percentage of the serum levels were found to be within the target range while overdosing was often observed for β-lactam antibiotics, and linezolid tended to be often underused. The results demonstrate an appreciable potential for β-lactam savings while enabling optimal therapy.ConclusionsThe presented monitoring method provides high specificity and is very robust against various interferences. A fast and straightforward method, the developed routine ensures rapid turnaround time. Its application has been well received by participating ICUs and has led to an expanding number of hospital wards participating in ATDM.

scholarly journals A randomized trial of therapeutic drug monitoring of protease inhibitors in antiretroviral-experienced, HIV-1-infected patients

AIDS ◽  
2009 ◽  
Vol 23 (3) ◽  
pp. 357-368 ◽  
Author(s):  
Lisa M Demeter ◽  
Hongyu Jiang ◽  
A Lisa Mukherjee ◽  
Gene D Morse ◽  
Robin DiFrancesco ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Randomized Trial ◽  
Protease Inhibitors ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Hiv 1

scholarly journals Scientific Programming with High Performance Fortran: A Case Study Using the xHPF Compiler

1997 ◽  
Vol 6 (1) ◽  
pp. 127-152
Author(s):  
Eric De Sturler ◽  
Volker Strumpen
Keyword(s):  
High Performance ◽  
Parallel Implementation ◽  
Gaussian Elimination ◽  
Primary Objective ◽  
Matrix Product ◽  
Dense Matrix ◽  
High Performance Fortran ◽  
Partial Pivoting ◽  
Intel Paragon

Recently, the first commercial High Performance Fortran (HPF) subset compilers have appeared. This article reports on our experiences with the xHPF compiler of Applied Parallel Research, version 1.2, for the Intel Paragon. At this stage, we do not expect very High Performance from our HPF programs, even though performance will eventually be of paramount importance for the acceptance of HPF. Instead, our primary objective is to study how to convert large Fortran 77 (F77) programs to HPF such that the compiler generates reasonably efficient parallel code. We report on a case study that identifies several problems when parallelizing code with HPF; most of these problems affect current HPF compiler technology in general, although some are specific for the xHPF compiler. We discuss our solutions from the perspective of the scientific programmer, and presenttiming results on the Intel Paragon. The case study comprises three programs of different complexity with respect to parallelization. We use the dense matrix-matrix product to show that the distribution of arrays and the order of nested loops significantly influence the performance of the parallel program. We use Gaussian elimination with partial pivoting to study the parallelization strategy of the compiler. There are various ways to structure this algorithm for a particular data distribution. This example shows how much effort may be demanded from the programmer to support the compiler in generating an efficient parallel implementation. Finally, we use a small application to show that the more complicated structure of a larger program may introduce problems for the parallelization, even though all subroutines of the application are easy to parallelize by themselves. The application consists of a finite volume discretization on a structured grid and a nested iterative solver. Our case study shows that it is possible to obtain reasonably efficient parallel programs with xHPF, although the compiler needs substantial support from the programmer.

High-Performance Liquid Chromatographic Determination of Memantine in Human Urine Following Solid-Phase Extraction and Precolumn Derivatization

2013 ◽  
Vol 96 (6) ◽  
pp. 1302-1307 ◽  
Author(s):  
Karim Michail ◽  
Hoda Daabees ◽  
Youssef Beltagy ◽  
Magdy Abd Elkhalek ◽  
Mona Khamis
Keyword(s):  
Human Urine ◽  
High Performance ◽  
Solid Phase ◽  
Internal Standard ◽  
Chromatographic Determination ◽  
Therapeutic Drug ◽  
Time Interval ◽  
Precolumn Derivatization ◽  
Uv Detector

Abstract A validated HPLC-UV method is presented for the quantification of urinary memantine hydrochloride, a novel medication approved to treat moderate and advanced cases of Alzheimer's disease. The drug and amantadine hydrochloride, the internal standard, were extracted from human urine using SPE. The extract was then buffered and derivatized at room temperature using o-phthalaldehyde in the presence of N-acetyl-L-cyteine. Chromatographic separation of the formed derivatives was achieved on a C18 column using methanol–water mobile phase adjusted to pH 7 and pumped isocratically at 1 mL/min. The UV detector was set at 340 nm. The chromatographic run time did not exceed 10 min. The LOD and LOQ were 8 and 20 ng/mL, respectively. The RSDs for intraday and interday precisions did not exceed 5.5%. The method was used to monitor memantine hydrochloride in human urine in order to determine an appropriate sampling interval for future noninvasive therapeutic drug monitoring. The assay could also be applied to the determination of amantadine. The described assay showed that a postdosing time interval of 25–75 h seems adequate for sampling and monitoring memantine in urine.

scholarly journals Pharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patients

2020 ◽  
Vol 19 (4) ◽  
pp. 20-31
Author(s):  
E. A. Litvin ◽  
D. T. Utalieva ◽  
D. Yu. Kachanov ◽  
A. V. Pshonkin ◽  
M. Ya. Yadgarov ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Medical Research ◽  
High Performance ◽  
Plasma Concentrations ◽  
Neuroblastoma Cells ◽  
Research Center ◽  
Therapeutic Drug ◽  
Pediatric Hematology ◽  
National Medical

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of > 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.

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