Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy.

PURPOSE: Lamotrigine (LTG) is used to treat epilepsy. The variability of LTG pharmacokinetics among individuals may be attributed to polymorphisms in the genes of uridine diphosphate glucuronosyltransferases (UGTs) 1A4 and UGT2B7 and/or combination with other drugs. In this study, we evaluated the association between LTG concentrations and patient characteristics such as genetic polymorphisms and the co-administration of antiepileptic drugs. METHODS: We recruited 122 patients with epilepsy. LTG concentrations were measured in blood samples from each patient under steady-state condition. We assessed the influence of multiple factors on LTG concentrations and derived a formula for predicting LTG concentrations using multiple linear regression analysis. RESULTS: We derived a formula to predict LTG concentrations that considers the daily dose of LTG, body weight, valproic acid concentration, phenytoin co-administration, and the co-administration of phenobarbital and/or carbamazepine as well as UGT1A4 142T>G and UGT2B7 -161C>T polymorphisms (adjusted coefficients of determination R (2) = 0.734). Furthermore, we used this formula to reveal a strong positive correlation between measured and predicted LTG concentrations (r (2) = 0.76, p < 0.001). CONCLUSION: We derived a formula that will be useful in clinical practice for predicting LTG concentrations in patients with epilepsy.

Influence of Genetic Polymorphisms and Concomitant Anxiolytic Doses on Antidepressant Maintenance Doses in Japanese Patients with Depression.

To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.

The effects of breast density on the benefits of mammograms with adjunctive ultrasonography in breast screening.

OBJECTIVE: Various efforts have been made to improve the accuracy of breast cancer screening. This study aimed to report differences in the contribution of ultrasonography to cancer screening assessments of dense and non-dense breasts. METHODS: The participants in this study were 29,640 Japanese women in their 40 s who underwent breast cancer screening at the Iwate Cancer Society between 2018 and 2021. This included women who chose mammography alone or mammography with adjunctive ultrasonography (overall assessment). They were classified into two groups according to the breast density in mammography: dense breasts and non-dense breasts. Recall rate, breast cancer detection rate, and positive predictive value of the two screening-type groups were evaluated for each breast density group. RESULTS: Of the 29,640 women analyzed, 18,861 (63.6%) underwent mammography alone and 10,779 (36.3%) were by overall assessments. The number of women recalled was higher in the overall assessment group than in the mammography-alone group (2.9% vs. 1.9%, p < 0.01). The proportion of women in whom breast cancer was detected was higher in the overall assessment group than in the mammography-alone group (0.31% [n = 33] vs. 0.15% [n = 28], p < 0.01). For non-dense breasts, there were no significant differences in either the recall rate or the breast cancer detection rate between those who underwent mammography alone and those who underwent overall assessment. Conversely, for dense breasts, the recall rate after mammography alone was lower than that after overall assessment (1.8% vs. 3.8%, p < 0.01), and the breast cancer detection rate was higher after overall assessment than after mammography alone (0.40% vs. 0.18%, p < 0.01). CONCLUSION: We found the benefits of adjunctive ultrasonography with mammography to differ depending on breast density. This could be used to tailor the selection of screening modalities to individuals.