Table 3.
Pharmacokinetic parameters of therapeutic nadroparin in critically ill patients.
| Parameters | All patients | CCr ≥ 50 (mL/min) | CCr ≥ 30-49 (mL/min) | CCr < 30 (mL/min) |
|---|---|---|---|---|
| Primary endpoint | ||||
| Patients (n) | 25 | 22 | 1 | 2 |
| Lowest anti-Xa (3-5 h) relative to Cmax (%) | 93 ± 5 (80-100) | 93 ± 5 (80-100) | 97 | 92 ± 4 (89-95) |
| Underestimated peak anti-Xa activities 3 h and 5 h after injection,a n (%) | 0 (100) | 0 (88) | 0 (4) | 0 (8) |
| Secondary endpoints | ||||
| Patients (n) | 22 | 1 | 2b | |
| Cmax (IU/mL) | 0.98 ± 0.43 (0.39-2.33) | 1.00 ± 0.45 (0.39-2.33) | 0.92 | 0.77 ± 0.28 (0.57-0.97) |
| Cmin (IU/mL) | 0.66 ± 0.43 (0.08-2.01) | 0.69 ± 0.43 (0.19-2.01) | c | 0.41 ± 0.47 (0.08-0.74) |
| tmax (h) | 5.00 (2.50-7.00) | 5.25 (3.50-7.00) | 5.00 | 5.25 (3.00-7.00) |
| AUC (0-12 h) (h·IU/mL) | 10.3 ± 4.8 (3.9-25.3) | 10.3 ± 5.0 (3.9-25.3) | c | 10.3b |
| AUC (0-24 h) (h·IU/mL) | 7.3 | 7.3b | ||
| ka (h-1) | 0.216 ± 0.218 (0.037-0.956) | 0.186 ± 0.165 (0.037-0.720) | 0.161 | 0.569 ± 0.547 (0.182-0.956) |
| t½ absorption (h) | 5.9 ± 4.3 (0.7-18.8) | 6.3 ± 4.4 (1.0-18.8) | 4.3 | 2.3 ± 2.2 (0.7-3.8) |
| ke (h-1) | 0.072 ± 0.040 (0.006-0.172) | 0.071 ± 0.041 (0.006-0.172) | c | 0.078 ± 0.033 (0.054-0.101) |
| t½ elimination (h) | 18.1 ± 25.1 (4.0-120.9) | 18.8 ± 26.2 (4.0-120.9) | c | 9.8 ± 4.2 (6.8-12.8) |
Data are presented as arithmetic mean ± SD (range), except for values of tmax, which are presented as median (range).
AUC, area under the anti-Xa activity vs time curve from injection, 0 to 12 hours or 24 hours; CCr, creatinine clearance (urine creatinine); Cmax, the actual maximal peak anti-Xa activity; Cmin, trough plasma activity; ka, the apparent absorption rate constant; ke, the apparent elimination rate constant; t½ absorption, the apparent absorption half-life; t½ elimination, the apparent elimination half-life; tmax, the time of actual peak anti-Xa activity (Cmax).
Underestimated if ([lowest measured anti-Xa in interval 3 to 5 hours]/[Cmax])× 100% is <80%.
CCr < 30 mL/min: AUC (0-24 hours) for patient with once-daily nadroparin (57% of standard dose) and AUC (0-12 hours) for patient with twice-daily nadroparin (109% of standard dose).
Pharmacokinetic parameters from elimination phase are missing in 1 patient because of incomplete follow-up (acute surgery).