Table Appendix II.
Studies evaluating the impact of obesity on volume of distribution (V)
| Drug | Subjects’ TBW, kg mean ± SD (range) | Central volume (Vc), l, mean ± SD | Size descriptors considered | Best descriptor | Correlation and direction or change in OBJ |
|---|---|---|---|---|---|
| Alprazolam [74] | Normal = 63.3 ± 2.9 | Normal = 73.1 ± 3.6 (SE)** | TBW/IBW/TBW | TBW | R2 = 0.67 |
| Obese = 111.6 ± 11.8 | Obese = 113.5 ± 11.4 (SE) | + ve | |||
| Lithium††[51] | Normal = 69.7 ± 9.3 | Normal 0.662 ± 0.157 | TBW/IBW/%IBW/LBW/ABW/ | BMI | R2 = 0.63 |
| Obese = 106.4 ± 22.1 | Obese = 0.418 ± 0.0858 | BMI/BSA/PNWT/HT/FFM | – ve | ||
| V = − 0.0125 x BMI + 0.9181 | |||||
| Dalteparin [52] | Normal = 69.7 ± 9.3 | Normal 8.36 (51.1%CV)NS | TBW/IBW/ABW | ABW | R2 = 0.55 |
| Obese = 106.4 ± 22.1 | Obese 12.39 (54.1%CV) | + ve | |||
| V = 0.33 x ABW − 14.1 | |||||
| Vancomycin [53] | NR | V = 0.219 x AGE (years) + 0.814 x TBW | TBW/IBW/%IBW | TBW + %IBW | R2 = 0.58 |
| + 0.536 x %IBW | + ve | ||||
| Propranolol [75] | Normal = 66.8 ± 11.3 | Normal = 198 ± 8* | TBW/IBW/BMI | TBW | R2 = 0.95+ ve |
| Obese = 136.5 ± 35.8 | Obese = 339 ± 22 | ||||
| Dexfenfluramine [76] | NR | Normal = 668.7 ± 139.6** | IBW/%IBW/BMI | %IBW | R2 = 0.30 |
| Obese = 969.7 ± 393.3 | + ve | ||||
| V = 6.113 x %IBW (± 2.2) + 88.5 (±273) | |||||
| Vancomycin [55] | Normal = 68 ± 6 | Normal = 46 ± 16NS | TBW/IBW | TBW | R2= 0.24 |
| Obese = 165 ± 46 | Obese = 52 ± 13 | + ve | |||
| Ifosfamide [56] | Normal = 64.2 (47.7–77.0) | Normal = 33.7 (17.8–50.6)* | TBW/IBW/%IBW | TBW & %IBW | R2= 0.37 |
| Obese = 76.8 (70.0–86.0) | Obese = 42.8 (35.5–51.9) | + ve | |||
| Bisoprolol [77] | Normal = 51 ± 4 | Normal = 135 ± 14*** | TBW/%IBW/BMI | %IBW | R2= 0.76+ ve |
| Obese = 91 ± 17 | Obese = 182 ± 26 | ||||
| Glyburide [37] | Normal = 135 ± 14 | Normal = 56.8 ± 60.3NS | TBW/IBW/BMI/FFM | BMI | R2= 0.31 |
| Obese = 182 ± 26 | Obese = 47.0 ± 47.0 | – ve | |||
| Caffeine[57] | Normal =66.9 ± 13.3 | Normal = 40.1 ± 13 | TBW/IBW/%IBW/LBW/ABW/ | ABW | R2 = 0.70 |
| Obese = 110.4 ± 19.2 | Obese = 49.9 ± 9.3 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| V = 0.7667 x ABW − 12.071 | |||||
| C-peptide [78] | Normal = 69.4 ± 11.4 | Normal = 4.18 ± 0.83*** | TBW/BMI/BSA | BSA | R2 = 0.23 |
| Obese = 107.9 ± 24.9 | Obese = 4.77 ± 1.27 | + ve | |||
| Males V = 1.92 x BSA + 0.64 | |||||
| Females V = 1.11 x BSA + 2.04 | |||||
| Ranitidine [58] | Normal = 54.8 ± 4.5 | Normal = 79.5 ± 14.0NS | TBW/IBW/LBW | IBW | R2 = 0.26 |
| Obese = 103.5 ± 10.4 | Obese = 83.3 ± 21.9 | + ve | |||
| Procainamide††[43] | Normal = 68.4 ± 11.5 | Normal = 150 ± 26.0NS | TBW/IBW/%IBW/LBW/ABW/ | IBW | R2 = 0.14 |
| Obese = 100.2 ± 17.3 | Obese = 158 ± 33.0 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| V = 1.0982 x IBW + 82.778 | |||||
| Carbamazepine†[59] | Normal = 62.2 ± 8.3*** | Normal = 60.7 ± 8.5 | TBW/IBW/%IBW/LBW/ABW/ | TBW | R2 = 0.86 |
| Obese = 111.4 ± 19.9 | Obese = 98.4 ± 26.9 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| V = 0.9031 x TBW + 0.2001 | |||||
| Desmethyldiazepam [79] | Normal = 67 (51–91) | Normal = 63 (38–119)*** | TBW/%IBW | TBW | R2 = 0.74 |
| Obese = 105 (77–197) | Obese = 159 (91–340) | + ve | |||
| Amikacin†[60] | 166.5 ± 36.9 | 27.4 ± 7.75 | TBW/IBW/%IBW/LBW/ABW/ | FFM | R2 = 0.35 |
| V = 0.3107 x FFM + 3.5167 | BMI/BSA/PNWT/HT/FFM | + ve | |||
| Theophylline [80] | Lean = 53 ± 5.5 | Lean = 22.5 ± 3.7** | TBW/IBW/%IBW/BMI | TBW | R2 = 0.56 |
| Control = 63 ± 10.5 | Control = 27.7 ± 8.1 | + ve | |||
| Obese = 81 ± 11.5 | Obese = 35.8 ± 5.1 | ||||
| Very obese = 115 ± 26.6 | Very obese = 42.4 ± 9.2 | ||||
| V = 11.9 + 0.262 x TBW | |||||
| Vancomycin†[61] | Normal = 74.6 ± 10.1 | Normal = 33.3 ± 3.4* | TBW/IBW/%IBW/LBW/ABW/ | ABW | R2 = 0.94 |
| Obese = 166 ± 44.0 | Obese = 50.2 ± 11.5 | BMI/BSA/PNWT/HT/FFM | |||
| V = 0.4927 x ABW − 1.9227 | + ve | ||||
| Phenytoin [81] | Normal = 67 ± 3 | Normal = 40.2 ± 1.9** | IBW/%IBW | IBW | R2 = 0.77 |
| Obese = 124 ± 10 | Obese = 82.2 ± 7.9 | + ve | |||
| Enoxaparin [62] | Normal = 65.9 ± 9.1 | Normal = 4.37*** | BSA/BMI/TBW/LBW/IBW/ | BSA | R2 = 0.60 |
| Obese = 99.6 ± 15.5 | Obese = 5.77 | %IBW | + ve | ||
| Enoxaparin [63] | 85.0 ± 20.5 | 3.67 l kg−1 (24.5 %CV) | TBW/IBW/LBW/ABW/BMI/ | TBW | = 47.6¶ |
| BSA/PNWT | |||||
| Remifentanil [67] | 88.7 ± 28.6 | Vc (l kg−1) = (0.121 x LBW) − 0.0713 | TBW/LBW | Vc = LBW | = 45¶¶ |
| Vp (l kg−1) = (0.165 x LBW) − 0.0713 | Vp = LBW | ||||
| p-Aminohippurate [68] | 99 ± 27 | V = (0.05 x TBW) + 5.58 | TBW/BSA/HT | TBW | >3.84¶ |
| Vinorelbine [71] | 66 | V = 2340 x (1 − 0.000849 x Plt count) | TBW/BSA/HT | None stat. sig. | >3.84¶ for BSA alone, |
| (39–114) | x (1 + 0.26 x SEX) | NOT included in final model | |||
| Etoposide [72] | Median = 65 | 5.6 l m−2 | TBW/BSA | BSA | = 26¶ |
| (35–106) | |||||
| Sufentanil [73] | 125.4 ± 23.3 | 37.1 (20%CV) | TBW/BMI/IBW/HT | None stat. sig. | N/A |
| (82–155) |
NR, not reported; OBJ, Objective function;
NS
, not significantly different between obese and normal group.
¶
Change in OBJ from baseline model.
¶¶
Combined change in OBJ with CL, Vc and V p scaled to LBW.
Δ
, Change in the objective function. Difference between obese and normal group where
*
P < 0.05;
**
P < 0.01;
***
P < 0.001.
†
Linear regression performed for this review (by B.G.) using raw data presented in the original paper.
‡
Data from original paper analysed by author (B.G.) using NONMEM v5 and G77 compiler.