This study is designed to assess the pharmacokinetics (PK) and safety of oseltamivir and its metabolite oseltamivir carboxylate in participants undergoing routine HD and CAPD for end-stage renal disease (ESRD). Participants will receive 6.5 and 6 weeks of the marketed oral oseltamivir suspension dosed according to the HD or CAPD schedule, respectively.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Oseltamivir will be given as marketed oral suspension, 30 mg after HD or CAPD treatment.
Unnamed facility
Christchurch, New Zealand
Maximum Plasma Concentration (Cmax) of Oseltamivir in HD Participants During Days 1 to 5
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in nanograms per milliliter (ng/mL).
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 1 (D1) dose
Cmax of Oseltamivir in HD Participants During Days 38 to 43
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from Day 38 (D38) dose
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
Cmax of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Area Under the Concentration-Time Curve (AUC) of Oseltamivir in HD Participants During Days 1 to 5
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the AUC was determined from 0 to 12 hours (AUC12) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in nanograms by hours per milliliter (ng\*h/mL).
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Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
AUC of Oseltamivir in HD Participants During Days 38 to 43
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 1 to 5
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5), and the AUC was determined from 0 to 42 hours (AUC42) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 dose
AUC of Metabolite Oseltamivir Carboxylate in HD Participants During Days 38 to 43
Plasma samples were obtained up to 90 hours post-dose during the second dose analysis (Days 38 to 43), and the AUC42 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D38 dose
Cmax of Oseltamivir in CAPD Participants During Days 1 to 6
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Cmax of Oseltamivir in CAPD Participants During Days 36 to 43
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from Day 36 (D36) dose
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
Cmax of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the maximum observed concentration was recorded. The Cmax was averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
AUC of Oseltamivir in CAPD Participants During Days 1 to 6
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
AUC of Oseltamivir in CAPD Participants During Days 36 to 43
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the AUC12 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 1 to 6
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6), and the AUC was determined from 0 to 48 hours (AUC48) and up to the last measurable concentration (AUClast). Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose
AUC of Metabolite Oseltamivir Carboxylate in CAPD Participants During Days 36 to 43
Plasma samples were obtained up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the AUC48 and AUClast were determined. Values were averaged among all participants and expressed in ng\*h/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120, 168 hours from D36 dose
Plasma Concentration of Oseltamivir by Timepoint in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49 hours from D1 and D38 dose AND at 90 hours from D1 dose AND at 114 hours from D38 dose
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first dose analysis (Days 1 to 5) and up to 114 hours post-dose during the second dose analysis (Days 38 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49 hours from D1 and D38 dose AND at 90 hours from D1 dose AND at 114 hours from D38 dose
Time to Maximum Plasma Concentration (Tmax) of Oseltamivir in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose
Tmax of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples were obtained up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from D1 and D38 dose
Oral Plasma Clearance (CL/F) of Oseltamivir in HD Participants
Plasma samples up to 12 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in liters per hour (L/h).
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D38 dose
CL/F of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples up to 42 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 and D38 dose
Renal Clearance (CLr) of Oseltamivir in HD Participants
Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose
CLr of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma and urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC42\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42 hours from D1 dose; urine samples 0 to 42 hours from D1 dose
Dialysis Clearance (CLd) of Metabolite Oseltamivir Carboxylate in HD Participants
Plasma samples up to 90 hours post-dose during the first (Days 1 to 5) and second (Days 38 to 43) dose analyses, in addition to dialyzer samples obtained on Days 3 and 40, were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 20, 32, 42, 48, 49, 90 hours from from D1 and D38 dose; dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40
Percentage of Oseltamivir Dose Excreted as Unchanged Drug in HD Participants
Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate drug excretion, computed as \[amount of drug excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 42 hours from D1 dose
Percentage of Oseltamivir Dose Excreted as Metabolite Oseltamivir Carboxylate in HD Participants
Urine samples up to 42 hours post-dose during the first dose analysis (Days 1 to 5) were used to calculate metabolite excretion, computed as \[amount of metabolite excreted divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 42 hours from D1 dose
Plasma Concentration of Metabolite Oseltamivir Carboxylate in Arterial and Venous Blood by Timepoint in HD Participants
Dialyzer samples were obtained up to 5 hours from the start of dialysis on Days 3 and 40 (corresponding to HD sessions 2 and 18). Arterial concentrations were estimated using the inflow to the dialyzer, and venous concentrations were estimated using the outflow from the dialyzer. The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Dialyzer samples 1, 2, 4, 5 hours from start of dialysis on Days 3 and 40
Plasma Concentration of Oseltamivir by Timepoint in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose
Plasma Concentration of Metabolite Oseltamivir Carboxylate by Timepoint in CAPD Participants
Plasma samples were obtained up to 120 post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). The concentration at each collection time was recorded and averaged among all participants and expressed in ng/mL.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose
Tmax of Oseltamivir in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose
Tmax of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43), and the observed time of maximum concentration was recorded. The Tmax following each dose was averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose
Elimination Rate Constant of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The elimination rate constant was calculated as \[natural log (ln)(2) divided by the half-life\] and expressed as inverse hours (1/h).
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose; urine samples 0 to 48 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose
Terminal Elimination Half-Life of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples were obtained up to 120 hours post-dose during the first dose analysis (Days 1 to 6) and up to 168 hours post-dose during the second dose analysis (Days 36 to 43). Urine and dialysate samples were also obtained up to 48 hours post-dose during the first dose analysis. The time required for the concentration to decrease by one-half was recorded and averaged among all participants and expressed in hours.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 and D36 dose AND at 168 hours from D36 dose; urine samples 0 to 48 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose
CL/F of Oseltamivir in CAPD Participants
Plasma samples up to 12 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 and D36 dose
CL/F of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples up to 48 hours post-dose during the first (Days 1 to 6) and second (Days 36 to 43) dose analyses were used to calculate apparent clearance adjusted for oral bioavailability. The CL/F with each dose was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 and D36 dose
CLr of Oseltamivir in CAPD Participants
Plasma and urine samples up to 12 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of drug excreted divided by the AUC12\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12 hours from D1 dose; urine samples 0 to 12 hours from D1 dose
CLr of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma and urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLr, computed as \[amount of metabolite excreted divided by the AUC48\]. The CLr was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48 hours from D1 dose; urine samples 0 to 48 hours from D1 dose
CLd of Metabolite Oseltamivir Carboxylate in CAPD Participants
Plasma samples up to 120 hours and dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate CLd, computed as \[amount of metabolite recovered in dialysate divided by the AUC over the dialysis interval\]. The CLd was averaged among all participants and expressed in L/h.
Time frame: Blood samples 0, 1, 2, 4, 8, 12, 24, 48, 72, 120 hours from D1 dose; dialysate samples 0 to 48 hours from D1 dose
Percentage of Oseltamivir Dose Renally Excreted as Unchanged Drug in CAPD Participants
Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of drug in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 48 hours from D1 dose
Percentage of Oseltamivir Dose Renally Excreted as Metabolite Oseltamivir Carboxylate in CAPD Participants
Urine samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate renal excretion, computed as \[amount of metabolite in urine divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Urine samples 0 to 48 hours from D1 dose
Percentage of Oseltamivir Dose Eliminated by Dialysis as Unchanged Drug in CAPD Participants
Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of drug in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Dialysate samples 0 to 48 hours from D1 dose
Percentage of Oseltamivir Dose Eliminated by Dialysis as Metabolite Oseltamivir Carboxylate in CAPD Participants
Dialysate samples up to 48 hours post-dose during the first dose analysis (Days 1 to 6) were used to calculate dialysis elimination, computed as \[amount of metabolite in dialysate divided by the oral oseltamivir dose\] multiplied by 100. The value was averaged among all participants and expressed as a percent of the oseltamivir dose administered.
Time frame: Dialysate samples 0 to 48 hours from D1 dose