TABLE 1.
Pharmacokinetic parameters of D‐3‐hydroxybutyrate and L‐3‐hydroxybutyrate after a single, oral dose of D,L‐3‐hydroxybutyrate in rats
| D‐3‐HB | L‐3‐HB | Total 3‐HB | |||||
|---|---|---|---|---|---|---|---|
| Parameter | Raw data | PK model | Raw data | PK model | Raw data | PK model | |
|
Controls, n = 6 0 mg/kg |
C max | 0.10 (0.07) | — | 0.01 (0.00) | — | 0.10 (0.07) | — |
| AUC0‐6 | 14 (3) | — | 1 (0) | — | 16 (3) | — | |
|
Low dose, n = 6 1579 mg/kg |
C max | 0.30 (0.03)a | 0.28 (0.03) | 1.88 (0.23)a | 1.64 (0.24) | 2.12 (0.23) | 1.96 (0.27) |
| t max | 85 (12) | 64 (10) | 135 (31) | 101 (10) | 135 (31) | 97 (9) | |
| t 1/2 | — | 129 (93) | — | 71 (6) | — | 75 (25) | |
| AUC0‐6 | 58 (10)a | 58 (10) | 380 (55)a | 338 (159) | 438 (62) | 406 (45) | |
| Clm | — | 7.04 (2.25) | — | 1.06 (0.11) | — | 0.95 (0.14) | |
| V 1 | — | 0.42 (0.15) | — | 0.04 (0.01) | — | 0.04 (0.01) | |
| k A | — | 2.04 (1.11) | — | 0.59 (0.05) | — | 0.79 (0.34) | |
|
Medium dose, n = 7 3159 mg/kg |
C max | 0.35 (0.11)a | 0.26 (0.07) | 1.92 (0.47)a | 1.61 (0.50) | 2.24 (0.50) | 1.87 (0.57) |
| t max | 167 (104) | 106 (70) | 227 (101) | 233 (95)b | 223 (104) | 175 (87) | |
| AUC0‐6 | 71 (17)a | 77 (18) | 454 (140)a | 416 (192) | 526 (155) | 467 (239) | |
|
High dose, n = 6 6317 mg/kg |
C max | 0.50 (0.13)abc | 0.36 (0.10) | 1.98 (0.26)a | 1.71 (0.41) | 2.41 (0.37) | 2.05 (0.45) |
| t max | 245 (94)b | 211 (120)b | 340 (49)bc | 332 (68)b | 340 (49) | 309 (80) | |
| AUC0‐6 | 106 (29)abc | 107 (26)b | 479 (87)a | 475 (91) | 585 (97) | 581 (96) | |
Note: Data are presented as mean (SD). For the low and medium dose group, the absorption and (part of) the elimination phases were observed, with Cmax reflecting peak concentrations. Upon high dose D,L‐3‐HB, we only observed the absorption phase, with C max possibly not reflecting peak concentrations. Based on the model performance, the distribution and elimination parameters could be estimated for the low dose group only. One‐way analysis of variance test followed by post hoc Bonferroni's multiple comparison test was used to test the 3‐HB enantiomer parameters for significant differences afrom control data; bfrom the low dose group; cfrom the medium dose group. The results were considered significantly different if P < .05. Abbreviations (in alphabetical order): AUC, area under the concentration‐time curve (min*mmol/L); Clm, metabolic clearance (L/h), C max, maximum concentration (mmol/L); PK, pharmacokinetic; k A, oral absorption rate constant (h−1); t max, time point at which C max is reached (min); t 1/2, elimination half‐life (min); V 1, volume of distribution to the central compartment (L/kg).