Table 2.
Results of analysis of variance for lamotrigine pharmacokinetic parameters in healthy individuals and patients with cirrhosis following a single 100 mg oral dose.
| Moberate cirrhosis(n = 12) | Severe cirrhosis without ascites(n = 12) | Severe cirrhosis without ascites(n = 12) | |||||
|---|---|---|---|---|---|---|---|
| Parameter (CI90%) | Control (n = 12)Geometric LSmean | Geometric LSmean | Geometric LSmean ratio (CI 90%) | Geometric LSmean | Geometric LSmean ratio° (CI 90%) | Geometric LSmean | Geometric LSmean ratio (CI 90%) |
| Cmax | 1.70 | 1.40 | 83%** | 1.58 | 93% | 1.56 | 92% |
| (µg ml−1) | (74%, 93%) | (81%, 106%) | (79%, 107%) | ||||
| tmax## | 1 | 1 | 0 | 1 | 0 | 2 | 1 |
| (h) | (0; 1) | (−1; 0) | (0; 5) | ||||
| AUC(0,∞) | 66.5 | 76.3 | 115% | 120 | 180%** | 197 | 297%*** |
| (µg ml−1 h) | (85%, 155%) | (127%, 255%) | (200%, 441%) | ||||
| CL/F | 0.36 | 0.29 | 81% | 0.22 | 60%* | 0.13 | 36%*** |
| (ml min−1 kg−1) | (61%, 106%) | (44%, 83%) | (25%, 52%) | ||||
| Vz/F | 0.98 | 1.06 | 109% | 1.21 | 123%** | 1.01 | 103% |
| (l kg−1) | (98%, 120%) | (109%, 139%) | (90%, 118%) | ||||
| t1/2 | 31.7 | 42.5 | 134%* | 64.5 | 204%*** | 90.9 | 287%*** |
| (h) | (103%, 175%) | (149%, 278%) | (202%, 408%) | ||||
#
median
°
median difference for tmax.
*
P < 0.10
**
P < 0.01
***
P < 0.001 compared with healthy volunteers. LS, least square; C
max, maximum plasma concentration; tmax, time to maximum plasma concentration, AUC∞, area under the plasma concentration-time curve from 0 to infinity; CL/F, apparent total clearance; Vz/F, apparent volume of distribution; t1/2, elimination half-life.