Session Type: 30min ePoster Review
Session Title: 30min ePoster Review
Authors(s): P.L. Chan (1), L. Mcfadyen (1), V.M. Hendrick (1), J. Le (2), J.S. Bradley (2, 3), E.B. Autry (4), E.E. Barsky (5), A. Quaye (1), S. Raber (6)
Authors Affiliations(s): (1) Pfizer, United Kingdom, (2) University of California at San Diego, United States, (3) Rady Children’s Hospital San Diego, United States, (4) University of Kentucky College of Pharmacy, United States, (5) Boston Children’s Hospital, United States, (6) Pfizer, United States
Background:
Population pharmacokinetic (PK) modelling have supported ceftaroline fosamil adult and paediatric dose selection. However, patients with severe underlying lung disease and potential for altered PK, including those with CF, were excluded from the original ceftaroline fosamil clinical trials. Independent of phase 3 trials, investigators have reported that the PK profile of ceftaroline may be altered in patients with CF.
Methods:Adult and paediatric PK data from published studies in patients with CF were combined with data from 21 adult and 6 paediatric trials of ceftaroline fosamil to characterise potential differences in structural PK parameters (ceftaroline clearance [CLc] and central volume of distribution [Vcc]) using NONMEM v7.4.3. Dose-normalised observed ceftaroline plasma concentrations were compared graphically for CF and non-CF patients. An existing population PK model was updated with CF patient data to test separate patient/indication effects (reference group: healthy and renally impaired volunteers [HV]) on CLc and Vcc for the CF population against a combined population of infected patients (community-acquired pneumonia [CAP], complicated skin and soft tissue infection [cSSTI], late-onset neonatal sepsis, or other suspected/confirmed acute infections), while retaining all prior covariates in the model.
Results:1273 subjects (<18 years, n=315; ≥18 years, n=958) contributing 9236 ceftaroline plasma concentrations were available from the existing model. An additional 35 patients with CF (6 to <18 years, n=23; ≥18 years, n=12) contributed 211 ceftaroline plasma concentrations. Observed dose-normalised ceftaroline plasma concentrations in paediatric and adult CF patients were consistent with age-matched patients with cSSTI, CAP and suspected/confirmed infection (Figure). With the inclusion of CF patient data, ceftaroline concentration–time data were adequately described using simultaneous two-compartment disposition models for ceftaroline fosamil and ceftaroline. Estimated patient/indication covariate effects on CLc were comparable in patients with CF and other infections (13% and 15% greater than HV), but Vcc was smaller for CF, and similar to HV versus other patient populations (3% versus 68% greater than HV, respectively).
Conclusions:Based on these combined data, differences in ceftaroline plasma PK between CF and other patient populations are small. Ceftaroline concentrations in CF airways and lungs remain to be evaluated.
Study sponsored by Pfizer.
Keyword(s): pharmacokinetics, ceftaroline fosamil, cystic fibrosisCOI Other: PLSC, LM, VMH, AQ and SR: employees of and shareholders in Pfizer. EBA: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JL: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JSB: No conflict of interest related to this analysis, except for the sharing of dataset published previously.EEB: Received institutional research funding for contributing CF patient PK data included in this analysis.
Session Type: 30min ePoster Review
Session Title: 30min ePoster Review
Authors(s): P.L. Chan (1), L. Mcfadyen (1), V.M. Hendrick (1), J. Le (2), J.S. Bradley (2, 3), E.B. Autry (4), E.E. Barsky (5), A. Quaye (1), S. Raber (6)
Authors Affiliations(s): (1) Pfizer, United Kingdom, (2) University of California at San Diego, United States, (3) Rady Children’s Hospital San Diego, United States, (4) University of Kentucky College of Pharmacy, United States, (5) Boston Children’s Hospital, United States, (6) Pfizer, United States
Background:
Population pharmacokinetic (PK) modelling have supported ceftaroline fosamil adult and paediatric dose selection. However, patients with severe underlying lung disease and potential for altered PK, including those with CF, were excluded from the original ceftaroline fosamil clinical trials. Independent of phase 3 trials, investigators have reported that the PK profile of ceftaroline may be altered in patients with CF.
Methods:Adult and paediatric PK data from published studies in patients with CF were combined with data from 21 adult and 6 paediatric trials of ceftaroline fosamil to characterise potential differences in structural PK parameters (ceftaroline clearance [CLc] and central volume of distribution [Vcc]) using NONMEM v7.4.3. Dose-normalised observed ceftaroline plasma concentrations were compared graphically for CF and non-CF patients. An existing population PK model was updated with CF patient data to test separate patient/indication effects (reference group: healthy and renally impaired volunteers [HV]) on CLc and Vcc for the CF population against a combined population of infected patients (community-acquired pneumonia [CAP], complicated skin and soft tissue infection [cSSTI], late-onset neonatal sepsis, or other suspected/confirmed acute infections), while retaining all prior covariates in the model.
Results:1273 subjects (<18 years, n=315; ≥18 years, n=958) contributing 9236 ceftaroline plasma concentrations were available from the existing model. An additional 35 patients with CF (6 to <18 years, n=23; ≥18 years, n=12) contributed 211 ceftaroline plasma concentrations. Observed dose-normalised ceftaroline plasma concentrations in paediatric and adult CF patients were consistent with age-matched patients with cSSTI, CAP and suspected/confirmed infection (Figure). With the inclusion of CF patient data, ceftaroline concentration–time data were adequately described using simultaneous two-compartment disposition models for ceftaroline fosamil and ceftaroline. Estimated patient/indication covariate effects on CLc were comparable in patients with CF and other infections (13% and 15% greater than HV), but Vcc was smaller for CF, and similar to HV versus other patient populations (3% versus 68% greater than HV, respectively).
Conclusions:Based on these combined data, differences in ceftaroline plasma PK between CF and other patient populations are small. Ceftaroline concentrations in CF airways and lungs remain to be evaluated.
Study sponsored by Pfizer.
Keyword(s): pharmacokinetics, ceftaroline fosamil, cystic fibrosisCOI Other: PLSC, LM, VMH, AQ and SR: employees of and shareholders in Pfizer. EBA: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JL: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JSB: No conflict of interest related to this analysis, except for the sharing of dataset published previously.EEB: Received institutional research funding for contributing CF patient PK data included in this analysis.
Session Type: 30min ePoster Review
Session Title: 30min ePoster Review
Authors(s): P.L. Chan (1), L. Mcfadyen (1), V.M. Hendrick (1), J. Le (2), J.S. Bradley (2, 3), E.B. Autry (4), E.E. Barsky (5), A. Quaye (1), S. Raber (6)
Authors Affiliations(s): (1) Pfizer, United Kingdom, (2) University of California at San Diego, United States, (3) Rady Children’s Hospital San Diego, United States, (4) University of Kentucky College of Pharmacy, United States, (5) Boston Children’s Hospital, United States, (6) Pfizer, United States
Background:
Population pharmacokinetic (PK) modelling have supported ceftaroline fosamil adult and paediatric dose selection. However, patients with severe underlying lung disease and potential for altered PK, including those with CF, were excluded from the original ceftaroline fosamil clinical trials. Independent of phase 3 trials, investigators have reported that the PK profile of ceftaroline may be altered in patients with CF.
Methods:Adult and paediatric PK data from published studies in patients with CF were combined with data from 21 adult and 6 paediatric trials of ceftaroline fosamil to characterise potential differences in structural PK parameters (ceftaroline clearance [CLc] and central volume of distribution [Vcc]) using NONMEM v7.4.3. Dose-normalised observed ceftaroline plasma concentrations were compared graphically for CF and non-CF patients. An existing population PK model was updated with CF patient data to test separate patient/indication effects (reference group: healthy and renally impaired volunteers [HV]) on CLc and Vcc for the CF population against a combined population of infected patients (community-acquired pneumonia [CAP], complicated skin and soft tissue infection [cSSTI], late-onset neonatal sepsis, or other suspected/confirmed acute infections), while retaining all prior covariates in the model.
Results:1273 subjects (<18 years, n=315; ≥18 years, n=958) contributing 9236 ceftaroline plasma concentrations were available from the existing model. An additional 35 patients with CF (6 to <18 years, n=23; ≥18 years, n=12) contributed 211 ceftaroline plasma concentrations. Observed dose-normalised ceftaroline plasma concentrations in paediatric and adult CF patients were consistent with age-matched patients with cSSTI, CAP and suspected/confirmed infection (Figure). With the inclusion of CF patient data, ceftaroline concentration–time data were adequately described using simultaneous two-compartment disposition models for ceftaroline fosamil and ceftaroline. Estimated patient/indication covariate effects on CLc were comparable in patients with CF and other infections (13% and 15% greater than HV), but Vcc was smaller for CF, and similar to HV versus other patient populations (3% versus 68% greater than HV, respectively).
Conclusions:Based on these combined data, differences in ceftaroline plasma PK between CF and other patient populations are small. Ceftaroline concentrations in CF airways and lungs remain to be evaluated.
Study sponsored by Pfizer.
Keyword(s): pharmacokinetics, ceftaroline fosamil, cystic fibrosisCOI Other: PLSC, LM, VMH, AQ and SR: employees of and shareholders in Pfizer. EBA: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JL: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JSB: No conflict of interest related to this analysis, except for the sharing of dataset published previously.EEB: Received institutional research funding for contributing CF patient PK data included in this analysis.
Session Type: 30min ePoster Review
Session Title: 30min ePoster Review
Authors(s): P.L. Chan (1), L. Mcfadyen (1), V.M. Hendrick (1), J. Le (2), J.S. Bradley (2, 3), E.B. Autry (4), E.E. Barsky (5), A. Quaye (1), S. Raber (6)
Authors Affiliations(s): (1) Pfizer, United Kingdom, (2) University of California at San Diego, United States, (3) Rady Children’s Hospital San Diego, United States, (4) University of Kentucky College of Pharmacy, United States, (5) Boston Children’s Hospital, United States, (6) Pfizer, United States
Background:
Population pharmacokinetic (PK) modelling have supported ceftaroline fosamil adult and paediatric dose selection. However, patients with severe underlying lung disease and potential for altered PK, including those with CF, were excluded from the original ceftaroline fosamil clinical trials. Independent of phase 3 trials, investigators have reported that the PK profile of ceftaroline may be altered in patients with CF.
Methods:Adult and paediatric PK data from published studies in patients with CF were combined with data from 21 adult and 6 paediatric trials of ceftaroline fosamil to characterise potential differences in structural PK parameters (ceftaroline clearance [CLc] and central volume of distribution [Vcc]) using NONMEM v7.4.3. Dose-normalised observed ceftaroline plasma concentrations were compared graphically for CF and non-CF patients. An existing population PK model was updated with CF patient data to test separate patient/indication effects (reference group: healthy and renally impaired volunteers [HV]) on CLc and Vcc for the CF population against a combined population of infected patients (community-acquired pneumonia [CAP], complicated skin and soft tissue infection [cSSTI], late-onset neonatal sepsis, or other suspected/confirmed acute infections), while retaining all prior covariates in the model.
Results:1273 subjects (<18 years, n=315; ≥18 years, n=958) contributing 9236 ceftaroline plasma concentrations were available from the existing model. An additional 35 patients with CF (6 to <18 years, n=23; ≥18 years, n=12) contributed 211 ceftaroline plasma concentrations. Observed dose-normalised ceftaroline plasma concentrations in paediatric and adult CF patients were consistent with age-matched patients with cSSTI, CAP and suspected/confirmed infection (Figure). With the inclusion of CF patient data, ceftaroline concentration–time data were adequately described using simultaneous two-compartment disposition models for ceftaroline fosamil and ceftaroline. Estimated patient/indication covariate effects on CLc were comparable in patients with CF and other infections (13% and 15% greater than HV), but Vcc was smaller for CF, and similar to HV versus other patient populations (3% versus 68% greater than HV, respectively).
Conclusions:Based on these combined data, differences in ceftaroline plasma PK between CF and other patient populations are small. Ceftaroline concentrations in CF airways and lungs remain to be evaluated.
Study sponsored by Pfizer.
Keyword(s): pharmacokinetics, ceftaroline fosamil, cystic fibrosisCOI Other: PLSC, LM, VMH, AQ and SR: employees of and shareholders in Pfizer. EBA: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JL: No conflict of interest related to this analysis, except for the sharing of dataset published previously.JSB: No conflict of interest related to this analysis, except for the sharing of dataset published previously.EEB: Received institutional research funding for contributing CF patient PK data included in this analysis.