Tenofovir, Emtricitabine Intracellular and Plasma, and Efavirenz Plasma Concentration Decay Following Drug Intake Cessation

Jackson, Akil; Moyle, Graeme; Watson, Victoria; Tjia, John; Ammara, Alieu; Back, David; Mohabeer, M; Gazzard, Brian; Boffito, Marta

doi:10.1097/qai.0b013e3182829bd0

Cited by 46 publications

(56 citation statements)

References 20 publications

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“…Emtricitabine PK parameters were within the ranges previously reported and are known to be unaffected by food intake or coadministration with rilpivirine (1, 7). Terminal elimination half-lives to the last measureable time point within 216 h for both nucleosides were considerably longer than those seen over 0 to 24 h (for tenofovir, 31 versus 13 h; for emtricitabine, 41 versus 6 h) and were also in agreement with values from the earlier study (7).…”

Section: Discussionsupporting

confidence: 81%

“…The tenofovir plasma exposure in the present study was higher than that obtained by Jackson et al in healthy volunteers stopping therapy (AUC 0 -last , 4,249 versus 2,895 ng · h/ml [7]) and was highlighted during the modeling process. The two studies were conducted at the same research unit, and the bioanalyses occurred at the same laboratory.…”

Section: Discussioncontrasting

confidence: 52%

“…Predictions of IC TFV-DP and FTC-TP concentrations from plasma data were also achieved utilizing modeling and simulation and prior information from a previous, similar study (7).…”

Section: Discussionmentioning

confidence: 99%

“…Plasma tenofovir, emtricitabine, and rilpivirine concentrations were determined using fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods (7,8). The lower limit of quantification (LLQ) was 0.5 ng/ml, and assay precision was Ͻ15% for all three drugs.…”

Section: Methodsmentioning

confidence: 99%

“…PBMCs were obtained as previously described (7). There was a technical issue encountered in generating the cell counts which meant that IC TFV-DP and FTC-TP data could not be determined by bioanalytical methods.…”

Section: Methodsmentioning

confidence: 99%

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Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation

Dickinson

Yapa²,

Jackson

et al. 2015

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 81%

Section: Discussioncontrasting

confidence: 52%

“…Predictions of IC TFV-DP and FTC-TP concentrations from plasma data were also achieved utilizing modeling and simulation and prior information from a previous, similar study (7).…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation

Dickinson

Yapa²,

Jackson

et al. 2015

Antimicrob Agents Chemother

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Population pharmacokinetics of tenofovir given as either tenofovir disoproxil fumarate or tenofovir alafenamide in an African population

Kawuma

Wasmann

Sinxadi

et al. 2023

CPT Pharmacom & Syst Pharma

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Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are prodrugs of the nucleotide analogue tenofovir, which acts intracellularly to inhibit HIV replication. Whereas TDF converts to tenofovir in plasma and may cause kidney and bone toxicity, TAF mostly converts to tenofovir intracellularly, so it can be administered at lower doses. TAF leads to lower tenofovir plasma concentrations and lower toxicity, but there are limited data on its use in Africa. We used data from 41 South African adults living with HIV from the ADVANCE trial and described, with a joint model, the population pharmacokinetics of tenofovir given as TAF or TDF. The TDF was modeled to appear in plasma as tenofovir with a simple first‐order process. Instead, two parallel pathways were used for a TAF dose: an estimated 32.4% quickly appeared as tenofovir into the systemic circulation with first‐order absorption, whereas the rest was sequestered intracellularly and released into the systemic circulation as tenofovir slowly. Once in plasma (from either TAF or TDF), tenofovir disposition followed two‐compartment kinetics and had a clearance of 44.7 L/h (40.2–49.5), for a typical 70‐kg individual. This semimechanistic model describes the population pharmacokinetics of tenofovir when dosed as either TDF or TAF in an African population living with HIV and can be used as a tool for exposure prediction in patients, and to simulate alternative regimes to inform further clinical trials.

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Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono‐infected pregnant women during labor by ultra‐performance liquid chromatography/tandem mass spectrometry

et al. 2020

Rapid Comm Mass Spectrometry

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Rationale: Tenofovir (TFV) is a first-line antiviral agent against hepatitis B virus (HBV)and is recommended for the prevention of mother-to-infant transmission of HBV. To study the distribution of TFV in umbilical cord plasma and amniotic fluid of HBVinfected pregnant women, a rapid and sensitive method for TFV determination was developed and validated. Methods:The quantification method was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The analytes were separated on an Acquity UPLC HSS T3 column under gradient elution with methanol and 0.01% ammonia solution in 10 mM ammonium acetate/water. This is the first reported method for the determination of TFV using alkaline rather than acidic mobile phases.Linearity, accuracy, precision, limit of quantification, specificity and stability were assessed.Results: Detection of TFV was achieved within 4 min. The calibration curves for TFV quantification showed excellent linearity in the range of 1-500 ng/mL. The intraand interbatch precision and accuracy ranged from −4.35% to 6.92%. This method was successfully applied to determination of samples from 50 HBV mono-infected women undergoing tenofovir disoproxil fumarate therapy. The mean concentrations of TFV in the umbilical cord and amniotic fluid samples were 29.2 (4.6-86) and 470.9 (156-902) ng/mL, respectively, which showed a moderate positive correlation (r = 0.5299, P<0.001). Conclusions:A simple, rapid but sensitive bioanalytical method to determine TFV concentration in both umbilical cord plasma and amniotic fluid using LC/MS/MS was developed and applied to HBV-infected women during labor who were undergoing TDF therapy, which will help us understand the efficacy and safety of tenofovir during pregnancy.

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Tenofovir, Emtricitabine Intracellular and Plasma, and Efavirenz Plasma Concentration Decay Following Drug Intake Cessation

Cited by 46 publications

References 20 publications

Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation

Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake Cessation

Population pharmacokinetics of tenofovir given as either tenofovir disoproxil fumarate or tenofovir alafenamide in an African population

Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono‐infected pregnant women during labor by ultra‐performance liquid chromatography/tandem mass spectrometry

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