Search

Your search keyword '"Back, David"' showing total 25 results
Start Over Author "Back, David" Journal antimicrobial agents and chemotherapy
25 results on '"Back, David"'

1. Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship with CYP2B6 c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

Author

Nightingale, Sam, primary, Chau, Tran Thi Hong, additional, Fisher, Martin, additional, Nelson, Mark, additional, Winston, Alan, additional, Else, Laura, additional, Carr, Daniel F., additional, Taylor, Steven, additional, Ustianowski, Andrew, additional, Back, David, additional, Pirmohamed, Munir, additional, Solomon, Tom, additional, Farrar, Jeremy, additional, Törok, M. Estée, additional, and Khoo, Saye, additional

Published
2016
Full Text
View/download PDF

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

Author

Dickinson, Laura, primary, Yapa, H. Manisha, additional, Jackson, Akil, additional, Moyle, Graeme, additional, Else, Laura, additional, Amara, Alieu, additional, Khoo, Saye, additional, Back, David, additional, Karolia, Zeenat, additional, Higgs, Chris, additional, and Boffito, Marta, additional

Published
2015
Full Text
View/download PDF

9. Pharmacokinetics of Lamivudine and Lamivudine-Triphosphate after Administration of 300 Milligrams and 150 Milligrams Once Daily to Healthy Volunteers: Results of the ENCORE 2 Study

Author

Else, Laura J., primary, Jackson, Akil, additional, Puls, Rebekah, additional, Hill, Andrew, additional, Fahey, Paul, additional, Lin, Enmoore, additional, Amara, Alieu, additional, Siccardi, Marco, additional, Watson, Victoria, additional, Tjia, John, additional, Emery, Sean, additional, Khoo, Saye, additional, Back, David J., additional, and Boffito, Marta, additional

Published
2012
Full Text
View/download PDF

14. Population Pharmacokinetic Modeling of the Association between 63396C→T Pregnane X Receptor Polymorphism and Unboosted Atazanavir Clearance

Author

Schipani, Alessandro, primary, Siccardi, Marco, additional, D'Avolio, Antonio, additional, Baietto, Lorena, additional, Simiele, Marco, additional, Bonora, Stefano, additional, Rodríguez Novoa, Sonia, additional, Cuenca, Lorena, additional, Soriano, Vincent, additional, Chierakul, Nitipatana, additional, Saguenwong, Natpratou, additional, Chuchuttaworn, Charoen, additional, Hoskins, Janelle M., additional, Dvorak, Anne M., additional, McLeod, Howard L., additional, Davies, Gerry, additional, Khoo, Saye, additional, Back, David J., additional, Di Perri, Giovanni, additional, and Owen, Andrew, additional

Published
2010
Full Text
View/download PDF

18. Intracellular Accumulation of Human Immunodeficiency Virus Protease Inhibitors

Author

Khoo, Saye H., primary, Hoggard, Patrick G., additional, Williams, Ian, additional, Meaden, E. Rhiannon, additional, Newton, Philippa, additional, Wilkins, Edmund G., additional, Smith, Alan, additional, Tjia, John F., additional, Lloyd, Judy, additional, Jones, Kevin, additional, Beeching, Nick, additional, Carey, Peter, additional, Peters, Barry, additional, and Back, David J., additional

Published
2002
Full Text
View/download PDF

21. Efavirenz and Metabolites in Cerebrospinal Fluid: Relationship with CYP2B6c.516G→T Genotype and Perturbed Blood-Brain Barrier Due to Tuberculous Meningitis

Author

Nightingale, Sam, Chau, Tran Thi Hong, Fisher, Martin, Nelson, Mark, Winston, Alan, Else, Laura, Carr, Daniel F., Taylor, Steven, Ustianowski, Andrew, Back, David, Pirmohamed, Munir, Solomon, Tom, Farrar, Jeremy, Törok, M. Estée, and Khoo, Saye

Abstract

ABSTRACTEfavirenz (EFZ) has been associated with neuropsychiatric side effects. Recently, the 8-hydroxy-EFZ (8OH-EFZ) metabolite has been shown to be a potent neurotoxin in vitro, inducing neuronal damage at concentrations of 3.3 ng/ml. EFZ induced similar neuronal damage at concentrations of 31.6 ng/ml. We investigated the effect of genotype and blood-brain barrier integrity on EFZ metabolite concentrations in cerebrospinal fluid (CSF). We measured CSF drug concentrations in subjects from two separate study populations: 47 subjects with tuberculous meningitis (TBM) coinfection in Vietnam receiving 800 mg EFZ with standard antituberculous treatment and 25 subjects from the PARTITION study in the United Kingdom without central nervous system infection receiving 600 mg EFZ. EFZ and metabolite concentrations in CSF and plasma were measured and compared with estimates of effectiveness and neurotoxicity from available published in vitroand in vivodata. The effect of the CYP2B6c.516G→T genotype (GG genotype, fast EFV metabolizer status; GT genotype, intermediate EFV metabolizer status; TT genotype, slow EFV metabolizer status) was examined. The mean CSF concentrations of EFZ and 8OH-EFZ in the TBM group were 60.3 and 39.3 ng/ml, respectively, and those in the no-TBM group were 15.0 and 5.9 ng/ml, respectively. Plasma EFZ and 8OH-EFZ concentrations were similar between the two groups. CSF EFZ concentrations were above the in vitrotoxic concentration in 76% of samples (GG genotype, 61%; GT genotype, 90%; TT genotype, 100%) in the TBM group and 13% of samples (GG genotype, 0%; GT genotype, 18%; TT genotype, 50%) in the no-TBM group. CSF 8OH-EFZ concentrations were above the in vitrotoxic concentration in 98% of the TBM group and 87% of the no-TBM group; levels were independent of genotype but correlated with the CSF/plasma albumin ratio. Potentially neurotoxic concentrations of 8OH-EFZ are frequently observed in CSF independently of the CYP2B6genotype, particularly in those with impaired blood-brain barrier integrity.

Published
2016
Full Text
View/download PDF

23. Raltegravir Is a Substrate for SLC22A6: a Putative Mechanism for the Interaction between Raltegravir and Tenofovir

Author

Moss, Darren M., Kwan, Wai San, Liptrott, Neill J., Smith, Darren L., Siccardi, Marco, Khoo, Saye H., Back, David J., and Owen, Andrew

Abstract

ABSTRACTThe identification of transporters of the HIV integrase inhibitor raltegravir could be a factor in an understanding of the pharmacokinetic-pharmacodynamic relationship and reported drug interactions of raltegravir. Here we determined whether raltegravir was a substrate for ABCB1 or the influx transporters SLCO1A2, SLCO1B1, SLCO1B3, SLC22A1, SLC22A6, SLC10A1, SLC15A1, and SLC15A2. Raltegravir transport by ABCB1 was studied with CEM, CEMVBL100, and Caco-2 cells. Transport by uptake transporters was assessed by using a Xenopus laevisoocyte expression system, peripheral blood mononuclear cells, and primary renal cells. The kinetics of raltegravir transport and competition between raltegravir and tenofovir were also investigated using SLC22A6-expressing oocytes. Raltegravir was confirmed to be an ABCB1 substrate in CEM, CEMVBL100, and Caco-2 cells. Raltegravir was also transported by SLC22A6 and SLC15A1 in oocyte expression systems but not by other transporters studied. The Kmand Vmaxfor SLC22A6 transport were 150 μM and 36 pmol/oocyte/h, respectively. Tenofovir and raltegravir competed for SLC22A6 transport in a concentration-dependent manner. Raltegravir inhibited 1 μM tenofovir with a 50% inhibitory concentration (IC50) of 14.0 μM, and tenofovir inhibited 1 μM raltegravir with an IC50of 27.3 μM. Raltegravir concentrations were not altered by transporter inhibitors in peripheral blood mononuclear cells or primary renal cells. Raltegravir is a substrate for SLC22A6 and SLC15A1 in the oocyte expression system. However, transport was limited compared to endogenous controls, and these transporters are unlikely to have a great impact on raltegravir pharmacokinetics.

Published
2010
Full Text
View/download PDF

24. Plasma and Intracellular (Peripheral Blood Mononuclear Cells) Pharmacokinetics of Once-Daily Raltegravir (800 Milligrams) in HIV-Infected Patients

Author

Moltó, José, Valle, Marta, Back, David, Cedeño, Samandhy, Watson, Victoria, Liptrott, Neill, Egan, Deirdre, Miranda, Cristina, Barbanoj, Manuel J., and Clotet, Bonaventura

Abstract

ABSTRACTThe aim of this study was to evaluate the plasma and intracellular pharmacokinetics of raltegravir in HIV-infected patients receiving once-daily raltegravir. Five HIV-infected patients on stable therapy with lopinavir-ritonavir monotherapy whose HIV-1 RNA load was <50 copies/ml were included in this open-label, pilot study. Raltegravir was added to the antiretroviral regimen at a dose of 800 mg once daily from days 0 to 10. On day 10, a full pharmacokinetic profile was obtained for each participant. Raltegravir concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were determined by high-performance liquid chromatography with a fluorescence detector and by liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. The values of the raltegravir pharmacokinetic parameters in plasma and PBMCs were calculated by noncompartmental analysis. Raltegravir was well tolerated, and all participants completed the study. No differences in the times to the maximum concentration of raltegravir in plasma or the raltegravir half-lives were observed between plasma and PBMCs. The geometric mean raltegravir maximum concentration, the concentration at the end of the dosing interval, and the area under the concentration-time curve during the dose interval in plasma versus PBMCs were 2,640 ng/ml (range, 887 to 10,605 ng/ml) versus 199 ng/ml (range, 82 to 857 ng/ml) (geometric mean ratio [GMR], 13.30; 95% confidence interval [CI], 3.11 to 56.89; P= 0.003); 89 ng/ml (range, 51 to 200 ng/ml) versus 7 ng/ml (range, 2 to 15 ng/ml) (GMR, 13.21; 95% CI, 3.94 to 44.26; P= 0.001); and 12,200 ng·h/ml (range, 5,152 to 30,130 ng·h/ml) versus 909 ng·h/ml (range, 499 to 2,189 ng·h/ml) (GMR, 13.43; 95% CI, 5.13 to 35.16; P< 0.001), respectively. Raltegravir does not accumulate in PBMCs, with intracellular concentrations being about 1/10 of the concentrations in plasma. Despite once-daily dosing, mean raltegravir concentrations at the end of the dosing interval in plasma and PBMCs exceeded the reported protein-binding-adjusted 95% inhibitory concentration (IC95) and IC50for wild-type viral strains, respectively.

Published
2010
Full Text
View/download PDF

25. Population pharmacokinetic modeling of the association between 63396C->T pregnane X receptor polymorphism and unboosted atazanavir clearance.

Author

Schipani A, Siccardi M, D'Avolio A, Baietto L, Simiele M, Bonora S, Rodríguez Novoa S, Cuenca L, Soriano V, Chierakul N, Saguenwong N, Chuchuttaworn C, Hoskins JM, Dvorak AM, McLeod HL, Davies G, Khoo S, Back DJ, Di Perri G, and Owen A

Subjects
ATP Binding Cassette Transporter, Subfamily B, ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Adult, Aged, Atazanavir Sulfate, Circadian Rhythm, Cytochrome P-450 CYP3A genetics, Female, Gene Frequency, Genotype, HIV Infections drug therapy, HIV Infections genetics, Humans, Liver-Specific Organic Anion Transporter 1, Male, Middle Aged, Oligopeptides therapeutic use, Organic Anion Transporters genetics, Pregnane X Receptor, Pyridines therapeutic use, Young Adult, Oligopeptides pharmacokinetics, Polymorphism, Single Nucleotide genetics, Pyridines pharmacokinetics, Receptors, Steroid genetics
Abstract

Atazanavir (ATV) plasma concentrations are influenced by CYP3A4 and ABCB1, which are regulated by the pregnane X receptor (PXR; NR1I2). PXR expression is correlated with CYP3A4 in liver in the absence of enzyme inducers. The PXR single nucleotide polymorphism (SNP) 63396C→T (rs2472677) alters PXR expression and CYP3A4 activity in vitro, and we previously showed an association of this polymorphism with unboosted ATV plasma concentrations. The aim of this study was to develop a population pharmacokinetic analysis to quantify the impact of 63396C→T and diurnal variation on ATV clearance. A population analysis was performed with 323 plasma samples from 182 randomly selected patients receiving unboosted ATV. Two hundred fifty-nine of the blood samples were collected at random time points, and 11 patients had a full concentration-time profile at steady state. Nonlinear mixed effects modeling was applied to explore the effects of PXR 63396C→T, patient demographics, and diurnal variation. A one-compartment model with first-order absorption and lag time best described the data. Population clearance was 19.7 liters/h with interpatient variability or coefficient of variation (CV) of 21.5%. Homozygosity for the T allele for PXR 63396 was associated with a 17.0% higher clearance that was statistically significant. Evening dosing was associated with 34% higher bioavailability than morning dosing. Patient demographic factors had no effect on ATV clearance. These data show an association of PXR 63396C→T and diurnal variation on unboosted ATV clearance. The association is likely to be mediated through an effect on hepatic PXR expression and therefore expression of its target genes (e.g., CYP3A4, SLCO1B1, and ABCB1), which are known to be involved in ATV clearance.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results