h. The neonates were administered two short courses of emtricitabine oral solution (each 3 mg/kg once daily × 4 days) during the first 3 months of life. The AUC observed in neonates who received a daily dose of 3 mg/kg of emtricitabine was similar to the AUC observed in pediatric subjects ages 3 months to 17 years who received a daily dose of emtricitabine as a 6 mg/kg oral solution up to 240 mg or as a 200 mg capsule (Table 6).
Table 6 Mean ± SD Pharmacokinetic Parameters by Age Groups for Pediatric Subjects and Neonates Receiving Emtriva Capsules or Oral Solution HIV-1-exposed Neonates HIV-1-infected Pediatric Subjects
Age 0–3 mo
(N=20)* 3–24 mo
(N=14) 25 mo–6 yr
(N=19) 7–12yr
(N=17) 13–17 yr
(N=27)
Formulation
Capsule (n) 0 0 0 10 26
Oral Solution (n) 20 14 19 7 1
Dose (mg/kg)† 3.1 (2.9–3.4) 6.1 (5.5–6.8) 6.1 (5.6–6.7) 5.6 (3.1–6.6) 4.4 (1.8–7.0)
Cmax (µg/mL) 1.6 ± 0.6 1.9 ± 0.6 1.9 ± 0.7 2.7 ± 0.8 2.7 ± 0.9
AUC (µg∙hr/mL) 11.0 ± 4.2 8.7 ± 3.2 9.0 ± 3.0 12.6 ± 3.5 12.6 ± 5.4
T1/2 (hr) 12.1 ± 3.1 8.9 ± 3.2 11.3 ± 6.4 8.2 ± 3.2 8.9 ± 3.3
Geriatric Patients
The pharmacokinetics of emtricitabine have not been fully eva luated in the elderly.
Patients with Impaired Renal Function
The pharmacokinetics of emtricitabine are altered in subjects with renal impairment [See Warnings and Precautions (5.4)]. In adult subjects with creatinine clearance less than 50 mL/min or with end-stage renal disease (ESRD) requiring dialysis, Cmax and AUC of emtricitabine were increased due to a reduction in renal clearance (Table 7). It is recommended that the dosing interval for Emtriva be modified in adult patients with creatinine clearance less than 50 mL/min or in adult patients with ESRD who require dialysis [See Dosage and Administration (2.5)]. The effects of renal impairment on emtricitabine pharmacokinetics in pediatric patients are not known.
Table 7 Mean ± SD Pharmacokinetic Parameters in Adult Subjects with Varying Degrees of Renal Function Creatinine Clearance (mL/min) >80
(N=6) 50–80
(N=6) 30–49
(N=6) <30
(N=5) ESRD*
<30
(N=5)
*
ESRD subjects requiring dialysis
†
NA = Not Applicable
Baseline creatinine clearance (mL/min) 107 ± 21 59.8 ± 6.5 40.9 ± 5.1 22.9 ± 5.3 8.8 ± 1.4
Cmax (µg/mL) 2.2 ± 0.6 3.8 ± 0.9 3.2 ± 0.6 2.8 ± 0.7 2.8 ± 0.5
AUC (µg∙hr/mL) 11.8 ± 2.9 19.9 ± 1.2 25.1 ± 5.7 33.7± 2.1 53.2 ± 9.9
CL/F (mL/min) 302 ± 94 168 ± 10 138 ± 28 99 ± 6 64 ± 12
CLr (mL/min) 213 ± 89 121 ± 39 69 ± 32 30 ± 11 NA†
Hemodialysis: Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
Patients with Hepatic Impairment
The pharmacokinetics of emtricitabine have not been studied in subjects with hepatic impairment, however, emtricitab
