Table Appendix I.
Studies evaluating the impact of obesity on clearance (CL)
| Drug | Subjects’ TBW, kg mean ± SD (range) | Clearance (CL), L h−1 mean ± SD | Size descriptors considered | Best descriptor | Correlation and direction or change in OBJ |
|---|---|---|---|---|---|
| Lithium†[51] | Normal = 69.7 ± 9.3 | Normal 1.38 ± 0.372** | TBW/IBW/%IBW/LBW/ABW/ | BMI | R2= 0.39 |
| Obese = 106.4 ± 22.1 | Obese = 1.97 ± 0.400 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| CL = 0.0275 x BMI + 0.846 | |||||
| Dalteparin [52] | Normal = 69.7 ± 9.3 | Normal 1.11 (25.2%CV)NS | TBW/IBW/ABW | TBW | R2= 0.39 |
| Obese = 106.4 ± 22.1 | Obese 1.3 (45.4%CV) | + ve | |||
| Vancomycin [53] | Not reported | CL ml min-1= 2.939 – 0.012 x AGE (years) | TBW/IBW/%IBW | TBW | R2 = NR |
| − 0.009 × TBW (kg) − 0.68 x SCr (mg dl−1) | – ve | ||||
| Busulphan [54] | Not reported | (BMI <18 = 9.96 ± 2.04 | TBW/BSA/ABW/IBW/HT/ | TBW | R2 = 0.30 |
| BMI 18–26.9 = 8.55 ± 2.7)*** | BSA/BMI | + ve | |||
| (BMI 27–35 = 13.4 ± 3.18 | |||||
| BMI >35 = 15.0 ± 2.82) | |||||
| Vancomycin [55] | Normal = 68 ± 6 | Normal = 4.62 ± 1.32*** | TBW/IBW | TBW | R2 = 0.90 |
| Obese = 165 ± 46 | Obese = 11.8 ± 4.62 | + ve | |||
| Ifosfamide [56] | Normal = 64.2 (47.7–77.0) | Normal = 4.33 (3.19–11.3)NS | TBW/IBW/%IBW | IBW | R2 = 0.49 |
| Obese = 76.8 (70.0–86.0) | Obese = 4.56 (3.9–5.50) | + ve | |||
| Doxorubicin [42] | Normal = 66 ± 14 | Normal = 94.1 ± 15.4 | TBW/IBW/%IBW/BSA | % IBW | R2 = 0.56 |
| Overweight = 78 ± 15 | Overweight = 73.6 ± 16.8 | – ve | |||
| Obese = 81 ± 14 | Obese = 53.5 ± 17.1* | ||||
| Glyburide [37] | Normal = 135 ± 14NS | Normal = 3.10 ± 1.98 | TBW/IBW/BMI/FFM | TBW | R2 = 0.34 |
| Obese = 182 ± 26 | Obese = 3.26 ± 2.19 | + ve | |||
| Caffeine†[57] | Normal = 66.9 ± 13.3NS | Normal = 4.96 ± 2.04 | TBW/IBW/%IBW/LBW/ABW/ | ABW | R2 = 0.31 |
| Obese = 110.4 ± 19.2 | Obese = 6.04 ± 2.97 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| CL = 0.1071 x ABW − 2.3647 | |||||
| Ranitidine [58] | Normal = 54.8 ± 4.5NS | Normal = 32.3 ± 6.1 | TBW/IBW/LBW | LBW | R2 = 0.16 |
| Obese = 103.5 ± 10.4 | Obese = 34.5 ± 6.9 | + ve | |||
| Procainamide†[43] | Normal = 68.4 ± 11.5NS | Normal = 41.9 ± 13.6 | TBW/IBW/%IBW/LBW/ABW/ | IBW | R2 = 0.24> |
| Obese = 100.2 ± 17.3 | Obese = 51.7 ± 9.17 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| CL = 0.6205 x IBW + 6.6157 | |||||
| Carbamazepine†[59] | Normal = 62.2 ± 8.3NS | Normal = 1.38 ± 0.276 | TBW/IBW/%IBW/LBW/ABW/ | IBW | R2 = 0.18 |
| Obese = 111.4 ± 19.9 | Obese = 1.19 ± 0.312 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| CL = 0.0159 x IBW + 0.2992 | |||||
| Amikacin[60] | 166.5 ± 36.9 | 8.57 ± 1.79 | TBW/IBW/%IBW/LBW/ABW/ | LBW | R2 = 0.45 |
| CL = 0.0429 x LBW + 6.2527 | BMI/BSA/PNWT/HT/FFM | + ve | |||
| Vancomycin[61] | Normal = 74.6 ± 10.1* | Normal = 4.85 ± 0.68 | TBW/IBW/%IBW/LBW/ABW/ | BSA | R2 = 0.98 |
| Obese = 166 ± 44.0 | Obese = 11.3 ± 3.88 | BMI/BSA/PNWT/HT/FFM | + ve | ||
| CL = 7.594 x BSA − 10.011 | |||||
| Enoxaparin [62] | Normal = 65.9 ± 9.1 | Normal = 0.74*** | BSA/BMI/TBW/LBW/IBW/ | BSA | R2 = 0.43 |
| Obese = 99.6 ± 15.5 | Obese = 0.99 | %IBW | + ve | ||
| Enoxaparin [63] | 85.0 ± 20.5 | 1.03 l h−1.70 kg−1 (6.80 %CV) | TBW/IBW/LBW/ABW/BMI/ | LBW | = 28.9¶ |
| BSA/PNWT | |||||
| Tobramycin¶¶[64] | 124.5 ± 19.5 | 0.136 l h−1 kg−1 (10.2%CV) | TBW/IBW/%IBW/LBW/ABW/ | PNWT | = 1336 |
| BMI/BSA/PNWT/HT/FFM | |||||
| Carboplatin [65] | (65–112) | 6.72 l h−1 kg−1 | IBW/TBW/ABW | ABW (CF estimated at 0.512) | > 3.84¶ |
| Tinzaparin [66] | Treatment group | CL = (− 2.13 SCr−1) – (0.006 %IBW−1) | IBW/%IBW/BMI | %IBW | = 5¶ |
| = 76.6 ± 18.4 | |||||
| Prophylaxis group | |||||
| = 70.5 ± 11.4 | |||||
| Remifentanil [67] | 88.7 ± 28.6 | CL (l min−1 kg−1) = (0.0185 x LBW) + 1.88 | TBW/LBW | LBW | = 45¶¶ |
| p-Aminohippurate [68] | 99 ± 27 | CL = (11.5 x BSA) − (0.107 x SCr) + 17.2 | TBW/BSA/HT | BSA | >3.84¶ |
| Lithium [69] | (44.5–111) | CL = (0.0093 x LBW) + (0.0885 x CLcr) | TBW/IBW/LBW/BSA | LBW | = 46¶ |
| For LBW alone | |||||
| Doxacurium [70] | NR | CL (ml min−1) = 2.11 x (1 − [0.001 x | TBW/IBW/%IBW/HT | %IBW | = 10.16¶ |
| %IBW]) x (1 + 0.00606 x [CLcr − 80]) | For %IBW alone | ||||
| Vinorelbine [71] | 66 | CL = 29.2 x BSA x (1 − 0.0009 x plat count) | TBW/BSA/HT | BSA | = 35¶ |
| (39–114) | + 6.7 x Wt/SCr) | For BSA alone | |||
| Etoposide [72] | Median = 65 | CL (ml min−1) = θ1 + 1.1 x (TBW/SCr) | TBW/BSA | TBW | = 46¶ |
| (35–106) | θ1 not reported | ||||
| Sufentanil [73] | 125.4 ± 23.3 | 76.2 (23%CV) | TBW/BMI/IBW/HT | None stat. sig. | N/A |
| (82–155) |
NR, not reported; SCr, serum creatinine; 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.