Integration of Atazanavir into an Existing Liquid Chromatography UV Method for Protease Inhibitors: Validation and Application

Keil, Kim M.; Hochreitter, Jill; DiFrancesco, Robin; Zingman, Barry S.; Reichman, Richard C.; Fischl, Margaret A.; Gripshover, Barbara; Morse, Gene D.

doi:10.1097/ftd.0b013e3180318ef3

Cited by 21 publications

(18 citation statements)

References 15 publications

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“…EFV and DRV were quantified using a previously published simultaneous high-performance liquid chromatography assay with slight modification. 9 Briefly, the method involved a liquid–liquid extraction of the plasma sample, followed by separation on a C8 Symmetry column (Waters Associates, Milford, MA) and detection using a Model 996 photodiode array detector (Waters Associates) to assure specificity. The lower limit of quantitation value was 100 ng/mL.…”

Section: Methodsmentioning

confidence: 99%

Lack of Pharmacokinetic Interactions Between Pitavastatin and Efavirenz or Darunavir/Ritonavir

Malvestutto

Morse

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background The drug–drug interactions between pitavastatin and darunavir/ritonavir (DRV/r) as well as pitavastatin and efavirenz (EFV) were examined in an open-label, parallel-arm, pharmacokinetic (PK) study in HIV-uninfected healthy volunteers. Methods Subjects received a pitavastatin dose of 2 mg for 4 days, followed by either EFV 600 mg (n = 14) or DRV/r 800/100 mg (n = 14) daily for 10 days, and pitavastatin 2 mg coadministered with EFV 600 mg or DRV/r 800/100 mg for 4 days. Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18. Results In the EFV arm, the geometric mean area under the concentration time curve (AUC0-τ) and Cmax of pitavastatin were 85.3 ng·h·mL−1 and 15.6 ng/mL, respectively, when given alone, versus 76 ng·h·mL−1 and 18.8 ng/mL when coadministered with EFV. The geometric mean ratio for pitavastatin with EFV versus alone was 0.89 [90% confidence interval (CI): 0.73 to 1.09] for AUC0-τ and 1.20 (90% CI: 0.79 to 1.83) for Cmax. In the DRV/r arm, AUC0-τ and Cmax were 62.8 ng·h·mL−1 and 24.0 ng/mL, respectively, when pitavastatin was administered alone, versus 56.9 ng·h·mL−1 and 23.2 ng/mL when coadministered with DRV/r. The geometric mean ratio for pitavastatin with DRV/r versus alone was 0.91 (90% CI: 0.78 to 1.06) for AUC0-τ and 0.93 (90% CI: 0.72 to 1.19) for Cmax. Conclusions There were no significant PK interactions between pitavastatin and EFV or DRV/r. No significant safety issues or lipid changes were noted.

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Section: Methodsmentioning

confidence: 99%

Lack of Pharmacokinetic Interactions Between Pitavastatin and Efavirenz or Darunavir/Ritonavir

Malvestutto

Morse

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Matrix variation [23] or matrix accuracy [24], defined as variation in different lots of matrix on assay accuracy, was evaluated using six different lots of healthy human plasma spiked with the analytes and assessing the spiked recovery.…”

Section: Methodsmentioning

confidence: 99%

A Simple LC–MS/MS Method for Determination of Kynurenine and Tryptophan Concentrations in Human Plasma from Hiv-Infected Patients

et al. 2013

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Background Indoleamine 2,3-dioxygenase, catalyzing tryptophan (Trp) metabolism through the kynurenine (Kyn) metabolic pathway, plays important roles in immune suppression and the CNS. In this article, we report a simple, rapid and specific LC–MS/MS method for accurate determination of Kyn and Trp concentrations in human plasma from HIV-infected patients. Results The human plasma sample (100 μl) was mixed with Kyn-d4 and Trp-d5 internal standards and then precipitated with trifluoroacetic acid. The supernatant was directly analyzed by LC–MS/MS. The assay using surrogate matrix calibrators was validated for precision, accuracy, matrix effect, extraction efficiency and stability. Some assay validation issues for endogenous substance bioanalysis using an LC–MS/MS method are discussed. Conclusion A simple, specific and reproducible LC–MS/MS method has been developed and validated for measuring Kyn and Trp in human plasma samples.

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“…Prior to routine use of the PI assay method for A5146, the PSL validated the method for rigor, accuracy, specificity, sensitivity, and reproducibility (21,22). The methods were submitted to the New York State Department of Health Clinical Laboratory Evaluation Program (NYS DOH CLEP), which approved the assay for use in the PSL.…”

Section: Methodsmentioning

confidence: 99%

Quality Assessment for Therapeutic Drug Monitoring in AIDS Clinical Trials Group (ACTG 5146): A Multicenter Clinical Trial

DiFrancesco¹,

Rosenkranz²,

Mukherjee³

et al. 2010

Therapeutic Drug Monitoring

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In a randomized trial, AIDS Clinical Trials Group (ACTG) protocol 5146 (A5146) investigated the use of TDM to adjust doses of HIV-1 protease inhibitors (PIs) in patients with prior virologic failure on PI-based therapy who were starting a new PI-based regimen. The overall percentage of “PI trough repeats”, such as rescheduled visits or redrawn PI trough specimens, increased from 2% to 5% to 10% as the process progressed from the clinical sites, the PSL, and the study team, respectively. Cumulatively, this represents a 17% rate of failure to obtain adequate PI trough sample. While targeting a turn-around of ≤ 7 days from sample receipt to a drug concentration report, 12% of the received specimens required a longer period to report concentrations. The implementation of dosing changes in the TDM arm were achieved within ≤7 days for 56% of the dose change events, and within ≤14 days for 77% of dose change events. This quality assurance analysis provides a valuable summary of the specific points in the TDM process that could be improved during a multicenter clinical trial including: [1] shortening the timeline of sample shipment from clinical site to the lab, [2] performing the collection of PI trough specimen within the targeted sampling window by careful monitoring of the last dose times and collection times by the clinicians [3] increasing patient adherence counseling to reduce the number of samples that are redrawn due to suspecting inconsistent adherence, and [4] decreasing the time to successful TDM-based dose adjustment. The application of some of these findings may also be relevant to single center studies or clinical TDM programs within a hospital.

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Integration of Atazanavir into an Existing Liquid Chromatography UV Method for Protease Inhibitors: Validation and Application

Cited by 21 publications

References 15 publications

Lack of Pharmacokinetic Interactions Between Pitavastatin and Efavirenz or Darunavir/Ritonavir

Lack of Pharmacokinetic Interactions Between Pitavastatin and Efavirenz or Darunavir/Ritonavir

A Simple LC–MS/MS Method for Determination of Kynurenine and Tryptophan Concentrations in Human Plasma from Hiv-Infected Patients

Quality Assessment for Therapeutic Drug Monitoring in AIDS Clinical Trials Group (ACTG 5146): A Multicenter Clinical Trial

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