Table 2.
Summary of fasiglifam plasma and urine pharmacokinetic parameter estimates following the administration of a single 50-mg dose of fasiglifam to subjects with varying degrees of renal function
| Renal function status | |||||
|---|---|---|---|---|---|
| Normal (n = 21) | Mild (n = 8) | Moderate (n = 8) | Severe (n = 8) | ESRD a (n = 8) | |
| Plasma pharmacokinetics | |||||
| T max (h) | 3.5 (2–8) | 3.1 (2–6) | 3.3 (2–4) | 2.8 (2–6) | 2.9 (1–6) |
| C max, u (ng/mL) | 3.8 (1.60) | 2.7 (0.72) | 2.7 (1.33) | 2.9 (1.35) | 2.7 (1.78) |
| C max (ng/mL) | 2306.2 (410.27) | 2510.0 (811.79) | 2352.9 (999.45) | 2115.0 (941.50) | 1920.0 (754.89) |
| AUC∞, u (ng·h/mL) | 93.8 (39.46) | 84.4 (41.75) | 75.6 (37.11) | 57.8 (42.49)b | 56.2 (37.96) |
| AUCt (ng·h/mL) | 56922.4 (23597.59) | 74298.1 (35300.40) | 61238.9 (29707.92) | 43533.1 (32163.52) | 36302.2 (17109.84) |
| AUC∞ (ng·h/mL) | 61463.4 (28463.44) | 77379.6 (37965.78) | 66776.5 (34699.57) | 47928.7 (41730.61)b | 40030.5 (21278.40) |
| CLu/F (L/ h) | 638.4 (317.30) | 788.0 (5634.0) | 938.5 (746.62) | 1306.8 (856.98) | 1392.3 (929.93) |
| CL/F (L/h) | 1.0 (0.49) | 0.9 (0.84) | 1.2 (1.19) | 1.7 (1.15)b | 1.6 (0.88) |
| t 1/2 (h) | 48.6 (24.13) | 34.5 (14.40) | 51.0 (19.49) | 38.8 (22.99)b | 53.9 (57.26) |
| Urine pharmacokinetics | |||||
| Ae(0–168) (ng) | 96476.6 (55826.49) | 175079.3 (124841.58) | 121740.4 (97466.30) | 60965.1 (41220.11) | NA |
| Fe (%) | 0.2 (0.11) | 0.4 (0.25) | 0.2 (0.20) | 0.1 (0.08) | NA |
| CLr (L/h) | 0.0 (0.00) | 0.0 (0.00) | 0.0 (0.00) | 0.0 (0.00) | NA |
T max data presented as mean (range). All other data presented as mean (standard deviation)
aESRD requiring dialysis
b n = 7
Ae (0–168) amount of drug excreted in urine from 0 to 168 hours, AUC ∞ area under the plasma-concentration time curve from time zero to infinity, AUC ∞, u area under the unbound plasma concentration time curve from time zero to infinity, AUCt AUC from time 0 to the time of last quantifiable concentration (t), calculated using the linear trapezoidal rule, CL/F oral clearance of fasiglifam, CLu/F oral clearance of unbound fasiglifam, CLr renal clearance, CrCl creatinine clearance, Cmax maximum plasma concentration, C max, u maximum observed unbound plasma concentration, ESRD end-stage renal disease, Fe Fraction of drug excreted in urine, NA not available, T max time to maximum plasma concentration, t 1/2 elimination half-life
Normal renal function, CrCl ≥90 mL/min; mild renal impairment, CrCl = 60 to <90 mL/min; moderate renal impairment, CrCl = 30 to <60 mL/min; severe renal impairment, CrCl<30 mL/min