The Experts below are selected from a list of 24252 Experts worldwide ranked by ideXlab platform
Stephanie E. Reuter - One of the best experts on this subject based on the ideXlab platform.
-
Population pharmacokinetics of ribavirin in lung transplant recipients and examination of current and alternative dosing regimens.
The Journal of antimicrobial chemotherapy, 2018Co-Authors: Eliza Jane Temple Milliken, Auke E S De Zwart, Jan-willem C. Alffenaar, Deborah Marriott, Annelies Riezebos-brilman, Ana Schteinman, Allan M. Evans, Allan R. Glanville, Erik A. M. Verschuuren, Stephanie E. ReuterAbstract:Background: Ribavirin is used in the treatment of respiratory paramyxovirus infection in lung transplant recipients; however, its pharmacokinetic profile in the transplant population is unknown despite the potential for alterations due to underlying pathology. Furthermore, the ability of current regimens to meet exposure targets has not been established. Objectives: This study examined the pharmacokinetics of ribavirin in a lung transplant population for which current and alternative dosing regimens were assessed. Methods: Population pharmacokinetic modelling was conducted in NONMEM using concentration-time data from 24 lung transplant recipients and 6 healthy volunteers. Monte Carlo simulation was used to assess the ability of dosing regimens to achieve pre-specified target concentrations. Results and conclusions: A three-compartment model with First-Order Elimination most adequately described ribavirin concentration-time data, with CLCR and patient type (i.e. lung transplant) identified as significant covariates in the model. Simulations indicate that current regimens achieve efficacious concentrations within 24 h of treatment initiation that increase to supra-therapeutic levels over the treatment period. A regimen of 8 mg/kg q6h orally for 48 h followed by 8 mg/kg q24h orally for the remainder of the treatment period was predicted to result in >90% of patients exhibiting concentrations within the defined target range throughout the entire treatment course. Additional work to formally establish target therapeutic concentrations is required; however, this study provides a valuable First step in determining optimal ribavirin treatment regimens for paramyxovirus infections in the lung transplant population.
Eliza Jane Temple Milliken - One of the best experts on this subject based on the ideXlab platform.
-
Population pharmacokinetics of ribavirin in lung transplant recipients and examination of current and alternative dosing regimens.
The Journal of antimicrobial chemotherapy, 2018Co-Authors: Eliza Jane Temple Milliken, Auke E S De Zwart, Jan-willem C. Alffenaar, Deborah Marriott, Annelies Riezebos-brilman, Ana Schteinman, Allan M. Evans, Allan R. Glanville, Erik A. M. Verschuuren, Stephanie E. ReuterAbstract:Background: Ribavirin is used in the treatment of respiratory paramyxovirus infection in lung transplant recipients; however, its pharmacokinetic profile in the transplant population is unknown despite the potential for alterations due to underlying pathology. Furthermore, the ability of current regimens to meet exposure targets has not been established. Objectives: This study examined the pharmacokinetics of ribavirin in a lung transplant population for which current and alternative dosing regimens were assessed. Methods: Population pharmacokinetic modelling was conducted in NONMEM using concentration-time data from 24 lung transplant recipients and 6 healthy volunteers. Monte Carlo simulation was used to assess the ability of dosing regimens to achieve pre-specified target concentrations. Results and conclusions: A three-compartment model with First-Order Elimination most adequately described ribavirin concentration-time data, with CLCR and patient type (i.e. lung transplant) identified as significant covariates in the model. Simulations indicate that current regimens achieve efficacious concentrations within 24 h of treatment initiation that increase to supra-therapeutic levels over the treatment period. A regimen of 8 mg/kg q6h orally for 48 h followed by 8 mg/kg q24h orally for the remainder of the treatment period was predicted to result in >90% of patients exhibiting concentrations within the defined target range throughout the entire treatment course. Additional work to formally establish target therapeutic concentrations is required; however, this study provides a valuable First step in determining optimal ribavirin treatment regimens for paramyxovirus infections in the lung transplant population.
Jeanpierre Sommadossi - One of the best experts on this subject based on the ideXlab platform.
-
population pharmacokinetics of nevirapine zidovudine and didanosine in human immunodeficiency virus infected patients
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Xiaojian Zhou, Lewis B Sheiner, Richard T Daquila, Michael Hughes, Martin S Hirsch, Margaret A Fischl, Victoria A Johnson, Maureen Myers, Jeanpierre SommadossiAbstract:The population pharmacokinetics of nevirapine (NVP), zidovudine (ZDV), and didanosine (ddI) were evaluated in a total of 175 patients infected with human immunodeficiency virus randomized to receive either a double combination of ZDV plus ddI or a triple combination of NVP plus ZDV plus ddI as a substudy of the AIDS Clinical Trials Group Protocol 241. Levels (approximating 3.5 determinations/patient) of the three drugs in plasma were measured during 44 of a total 48 weeks of study treatment, and a set of potential covariates was available for nonlinear mixed-effect modeling analysis. A one-compartment model with zero-Order input and First-Order Elimination was fitted to the NVP data. Individual oral clearance (CL) and volume of distribution (V) averaged 0.0533 liters/h/kg of body weight and 1.17 liters/kg, respectively. Gender was the only covariate which significantly correlated with the CL of NVP. ZDV and ddI data were described by a two-compartment model with zero-Order input and First-Order Elimination. Individual mean oral CL, VSS (volume of distribution at steady state), and V of ZDV were 1.84 liters/h/kg and 6.68 and 2.67 liters/kg, respectively, with body weight and age as correlates of CL and body weight as a correlate of VSS. The average individual oral CL, VSS, and V of ddI were 1.64 liters/h/kg and 3.56 and 2.74 liters/kg, respectively, with body weight as a significant correlate of both CL and VSS. The relative bioavailability (F) of ZDV and ddI in the triple combination compared to that in the double combination was also evaluated. No significant effects of the combination regimens on the F of ddI were detected (FTRIPLE = 1.05 and FDOUBLE = 1 by definition), but the F of ZDV was markedly reduced by the triple combination, being only 67.7% of that of the double combination. Large (>50%) intraindividual variability was associated with both ZDV and ddI pharmacokinetics. Individual cumulative area under the plasma drug level-time curve of the three drugs was calculated for the entire study period as a measure of drug exposure based on the individual data and the final-model estimates of structural and statistical parameters.
Lawrence Corey - One of the best experts on this subject based on the ideXlab platform.
-
population pharmacokinetics analysis of vrc01 an hiv 1 broadly neutralizing monoclonal antibody in healthy adults
mAbs, 2017Co-Authors: Yunda Huang, Lily Zhang, Julie E Ledgerwood, Nicole Grunenberg, Robert T Bailer, Abby Isaacs, Kelly E Seaton, Kenneth H Mayer, Edmund V Capparelli, Lawrence CoreyAbstract:ABSTRACTThe monoclonal antibody VRC01 targets the CD4 binding site of the human immunodeficiency virus (HIV)-1 envelope. In the clinical study HVTN 104 (NCT02165267), 84 HIV-uninfected adults received multiple-dose intravenous (IV) VRC01 (10, 20, 30 or 40 mg/kg) every 4 or 8 weeks or subcutaneous (SC) VRC01 (5 mg/kg) every 2 weeks, and were followed for 32 weeks. We conducted a population pharmacokinetics (popPK) analysis based on 1117 VRC01 serum concentrations using a 2-compartment PK model with First-Order Elimination; for SC VRC01 a depot compartment with a First-Order absorption rate constant was also included. All PK parameters were estimated with acceptable precision. Estimated bioavailability of SC VRC01 was 74%, with peak concentrations occurring 2–3 d after administration. For both IV and SC VRC01, population mean estimates for clearance (CL), central volume of distribution (Vc), inter-compartmental distribution clearance (Q) and peripheral volume of distribution (Vp) were 0.40 L/day, 1.94 L, 0....
Michael Hughes - One of the best experts on this subject based on the ideXlab platform.
-
population pharmacokinetics of nevirapine zidovudine and didanosine in human immunodeficiency virus infected patients
Antimicrobial Agents and Chemotherapy, 1999Co-Authors: Xiaojian Zhou, Lewis B Sheiner, Richard T Daquila, Michael Hughes, Martin S Hirsch, Margaret A Fischl, Victoria A Johnson, Maureen Myers, Jeanpierre SommadossiAbstract:The population pharmacokinetics of nevirapine (NVP), zidovudine (ZDV), and didanosine (ddI) were evaluated in a total of 175 patients infected with human immunodeficiency virus randomized to receive either a double combination of ZDV plus ddI or a triple combination of NVP plus ZDV plus ddI as a substudy of the AIDS Clinical Trials Group Protocol 241. Levels (approximating 3.5 determinations/patient) of the three drugs in plasma were measured during 44 of a total 48 weeks of study treatment, and a set of potential covariates was available for nonlinear mixed-effect modeling analysis. A one-compartment model with zero-Order input and First-Order Elimination was fitted to the NVP data. Individual oral clearance (CL) and volume of distribution (V) averaged 0.0533 liters/h/kg of body weight and 1.17 liters/kg, respectively. Gender was the only covariate which significantly correlated with the CL of NVP. ZDV and ddI data were described by a two-compartment model with zero-Order input and First-Order Elimination. Individual mean oral CL, VSS (volume of distribution at steady state), and V of ZDV were 1.84 liters/h/kg and 6.68 and 2.67 liters/kg, respectively, with body weight and age as correlates of CL and body weight as a correlate of VSS. The average individual oral CL, VSS, and V of ddI were 1.64 liters/h/kg and 3.56 and 2.74 liters/kg, respectively, with body weight as a significant correlate of both CL and VSS. The relative bioavailability (F) of ZDV and ddI in the triple combination compared to that in the double combination was also evaluated. No significant effects of the combination regimens on the F of ddI were detected (FTRIPLE = 1.05 and FDOUBLE = 1 by definition), but the F of ZDV was markedly reduced by the triple combination, being only 67.7% of that of the double combination. Large (>50%) intraindividual variability was associated with both ZDV and ddI pharmacokinetics. Individual cumulative area under the plasma drug level-time curve of the three drugs was calculated for the entire study period as a measure of drug exposure based on the individual data and the final-model estimates of structural and statistical parameters.