ABSTRACT
OBJECTIVE: To estimate and optimize the dosage regimens of lamotrigine for epileptic children with the utilization of Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic principle of antiepileptic drugs. METHODS: Population pharmacokinetic data of lamotrigine for epileptic children in China was obtained from the published literatures. Ten thousand times Monte Carlo simulation were performed for 25 dosing regimens for epileptic children aged 2 to 12 years and 33 dosing regimens for post-12-year-old epileptic children to obtain the steady-state concentration (css) and the probability of target attainment (PTA). Based on this, the rationality of the dosing regimens were evaluated and the optimal dosing regimen was screened. RESULTS: Within the recommended dosage range of lamotrigine for epileptic children aged 2 to 12 years, six of the nine pre-established maintenance-phase regimens were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window ranged from 80.54% to 90.69%, meanwhile the PTA that plateau concentrations distributed over the therapeutic window ranged from 0.41% to 12.50%, and the predicted mean of css ranged from 4.62 to 9.28 mg•L-1, so each was the optimization regimen. Among the 15 dosage regimens of lamotrigine for epileptic children over 12 years old, eleven of fifteen pre-established maintenance-phase regimens were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window ranged from 91.51% to 100.00%, the PTA that plateau concentrations distributed over the therapeutic window ranged from 0.00% to 8.49%, and the predicted mean of css ranged from 6.21 to 12.44 mg•L-1, so each was the optimization regimen. Interestingly, five off-label regimens of lamotrigine (12.5, 25, 37.5 mg, bid and 25, 50 mg, qd) in combination with valproic acid were found that the PTA that lamotrigine plateau concentrations distributed in therapeutic window was 100.00%, and the predicted mean of css ranged from 3.84 to 11.51 mg•L-1, which were superior to the recommended dosage (100-200 mg•d-1), indicating use with caution could be acceptable. CONCLUSION: In most cases, lamotrigine can be given according to drug instructions to obtain satisfactory therapeutic effect. However, some of off-label drug of use have certain rationality and necessity.
ABSTRACT
This study was aimed to investigate the serologic characteristics, genetic background and population distribution of B2 and AB2 subtype in Chinese ABO blood group. The classic blood group serological technology was used to detect ABO blood group of the propositus and their family members, the anti-B1 serum prepared by yourself was used to investigate the distribution of B1/B2 and AB1/AB2 subtype of the blood donor. The results indicated that the antigen of propositus was AB2 subtype and that of his child was B2 subtype. The anti-B1 antibody was detected in blood serum of propositus; the antigen of 3 from 2318 blood donors with B blood group were found to be B2 subtype, the antigen of 2 from 826 blood donors with AB blood group were found to be AB2 subtype. The investigation on propositus and the 3 B2 blood donor families showed that B2 antigen displays genetic characteristics of blood group. It is concluded that B2/AB2 subtype is from family inheritance, while B2 subtype is amounted to 0.129% in B blood group, and AB2 subtype is amounted to 0.224% in AB blood group.