TABLE 2.
Pharmacokinetic Parameters in Plasma and Excretion Parameters Obtained After IV Administration of Gadoquatrane
| Noncompartmental Analysis | Population Pharmacokinetic Analysis | |||
|---|---|---|---|---|
| 0.03 mmol Gd/kg BW IV Bolus Injection | 0.1 mmol Gd/kg BW IV Bolus Injection | 0.2 mmol Gd/kg BW IV Bolus Injection | ||
| Parameter, Unit | n = 6 | n = 6 | n = 6 | n = 98 |
| Cmax, μmol/L | 250 (11.8) | 948 (34.3) | 1780 (25.6) | N/A |
| Cmax,norm, kg/L | 8.28 (12.1) | 9.48 (34.4) | 8.92 (25.6) | N/A |
| C10, μmol/L | 188 (11.5) | 625 (11.8) | 1283 (13.1) | 675 (15.8)* |
| C20, μmol/L | 143 (11.9) | 473 (11.9) | 921 (13.7) | 490 (12.2)* |
| AUC, μmol·h/L | 293 (16.9) | 1020 (22.1) | 2050 (12.0) | 942 (16.6)†,‡ |
| AUCnorm, kg·h/L | 9.73 (17.2) | 10.2 (22.1) | 10.2 (12.0) | 9.42†,‡ |
| CL/BW, L/h/kg | 0.103 (17.2) | 0.0984 (22.1) | 0.0978 (12.0) | 0.108 (13.1)‡ |
| CLR/BW, L/h/kg | 0.105 (15.8) | 0.0945 (23.4) | 0.0715 (30.7) | N/A |
| t1/2,eff, h | 1.46 (10.5) | 1.54 (17.3) | 1.73 (5.84) | 1.52 (13.7)‡ |
| MRT, h | 2.11 (10.5) | 2.22 (17.3) | 2.50 (5.84) | 2.20 (13.7)‡ |
| Vss/BW, L/kg | 0.217 (13.5) | 0.219 (7.91) | 0.244 (14.0) | 0.237 (7.00)‡ |
| AE,urine (0–12 h), % of dose | 101 ± 5.24 (5.17)§ | 94.4 ± 3.64 (3.85)§ | 74.2 ± 18.0 (24.2)§,∥ | N/A |
| AE,urine (0–72 h), % of dose | 102 ± 5.15 (5.04)§ | 96.0 ± 3.33 (3.46)§ | 75.2 ± 18.1 (24.1)§,∥ | N/A |
| AE,feces (0–72 h), % of dose | 0.0418 ± 0.0281 (67.2)§ | 0.0538 ± 0.0427 (79.3)§,¶ | 0.0610 ± 0.0478 (78.4)§,¶ | N/A |
Data are geometric means followed by coefficients of variation (%) in parentheses unless indicated otherwise. Drug concentrations in plasma are based on Gd concentration.
The complete list of noncompartmental pharmacokinetic parameters is provided in Supplemental Digital Content, Chapter 7, http://links.lww.com/RLI/A877. Details of the population pharmacokinetic analysis are provided in Supplemental Digital Content, Chapter 5, http://links.lww.com/RLI/A877.
*Individual predicted concentration after bolus injection of 0.1 mmol Gd/kg BW, n = 13.
†AUC and AUCnorm calculated for the standard dose of 0.1 mmol Gd/kg BW, n = 19.
‡Data obtained after bolus injection as well as after 5-minute infusion was considered for parameter calculation; n = 98.
§Data are arithmetic means ± SD followed by coefficient of variation (%) in parentheses.
∥One participant had an exceptionally low recovery within the first 4 hours post dose, most likely due to procedural difficulties. Thus, the cumulated amounts are lower in this group than in the other dose groups.
¶N = 5 (Note: Some participants had no bowel movements during the sampling interval.)
AE,feces (0–72 h), amount of Gd excreted in feces within 72 hours; AE,urine(0-…h), amount of Gd excreted in urine within the specified time interval; AUC, area under the concentration-time curve from time zero to infinity after single dose administration; AUCnorm, AUC divided by dose/kg BW; BW, body weight; CL/BW, total body clearance of drug per kg BW; CLR/BW, renal body clearance of drug per kg BW; C10, drug concentration at 10 minutes after IV bolus injection; C20, drug concentration at 20 minutes after IV bolus injection; Cmax, maximum observed drug concentration after single dose administration; Cmax, norm, Cmax divided by dose per kg BW; IV, intravenous; MRT, mean residence time; n, number of evaluable participants; N/A, not applicable; t1/2,eff, effective half-life calculated based on the MRT, which was multiplied by the natural logarithm of 2. This half-life describes the overall effective elimination of the drug. Vss/BW, apparent volume of distribution at steady state per kg BW.