Table 4.
Parameter (units) | β-Hydroxybutyrate
|
Acetoacetate
|
||||
---|---|---|---|---|---|---|
140 mg/kg bw (n = 6c) | 357 mg/kg bw (n = 6d) | 714 mg/kg bw (n = 6) | 140 mg/kg bw (n = 6e) | 357 mg/kg bw (n = 6) | 714 mg/kg bw (n = 6) | |
AUC0-t (hr·mM) | 0.89 (28.49) | 2.85 (19.45) | 12.75 (25.93) | 1.15 (81.53) | 3.10 (32.28) | 6.66 (22.82) |
AUC0-inf (hr·mM) | 1.09 (35.79) | 4.00 (18.44) | 13.00 (24.70) | 2.06 (120.20) | 4.19 (33.39) | 7.80 (19.19) |
AUCt-inf (h mM) | 0.81 (9.88) | 0.77 (14.11) | 0.98 (1.98) | 0.60 (44.20) | 0.74 (6.73) | 0.85 (10.76) |
Cmax (mM) | 0.28 (45.28) | 1.00 (19.92) | 3.30 (25.89) | 0.23 (36.13) | 0.54 (10.23) | 1.19 (27.02) |
Tmax (h) | 1.50 (1.00–2.00) | 1.50 (1.00–3.00) | 2.50 (2.00–3.00) | 2.00 (1.00–3.00) | 2.50 (1.00–3.00) | 2.50 (2.00–4.00) |
Kel (1/h) | 0.5859 (60.91) | 0.3209 (56.88) | 0.9410 (21.02) | 0.2777 (103.20) | 0.1143 (84.38) | 0.0944 (50.41) |
T1/2 (h) | 1.61 (70.84) | 3.06 (73.25) | 0.77 (21.15) | 14.29 (163.10) | 8.23 (39.42) | 10.47 (74.19) |
CL/F (mg/h mM) | 11,946.25 (46.51) | 6093.05 (19.94) | 4179.06 (31.91) | 10,338.45 (61.78) | 6554.10 (36.67) | 6745.64 (21.10) |
Abbreviations: AUC = area under the curve; bw = body weight.
Data are presented as arithmetic mean (% coefficient of variation) with the exception of Tmax, which is presented as median (range) for Tmax.
The lower limit of quantitation for both β-hydroxybutyrate and acetoacetate (0.05 mM) was >5% of the Cmax obtained, and on average, less than three half-lives of the pharmacokinetic curve was characterized for individuals treated with the lowest dose of ketone monoester (140 mg/kg bw). As such, the analytical method used to detect the ketones may not have been sufficiently sensitive to measure concentrations at the later time points.
N = 4 for the parameters AUC0-inf, AUCt-inf, Kel, T1/2, CL/F.
N = 3 for the parameters AUC0-inf AUCt-inf, Kel, T1/2, CL/F.
N = 4 for the parameters AUC0-t, AUCt-inf, Kel, T1/2, CL/F.