ABSTRACT
Objectives@#：To describe the differences in long-term outcomes in Alzheimer’s disease (AD) patients according to initial dementia severity. @*Methods@#：A retrospective chart review of AD patients from a dementia clinic at the University Hospital in Korea was conducted from April 2010 to March 2017. There were 168 patients enrolled, who were divided into three groups based on initial Clinical Dementing Rating (CDR). There were 55 in the very mild group (CDR=0.5 ; mean age 80.64±6.57), 93 in the mild group (CDR=1 ; mean age 80.57±7.28) and 20 in the moderate group (CDR=2 ; mean age 83.00±9.07). Participants were treated with donepezil±memantine. The observation period was 2.44±0.50 years. Cognitive function and severity of dementia were initially assessed by the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) and were annually assessed by Mini-Mental State Exam (MMSE), CDR and CDR-Sum of boxes (CDR-SB). @*Results@#：The annual decline rate of MMSE score was -0.82 and those of very mild, mild, moderate groups were -0.63, -0.80, -1.96 respectively, while the annual change in CDR-SB score was 0.98, very mild group 0.86, mild group 1.03, moderate group 1.26. Education level, male, initial CDR were found to be significant potential factors in the annual change in MMSE, while initial CDR was a significant potential factor in the annual change in CDR-SB. @*Conclusion@#：It is meaningful that we studied long-term outcomes of anti-dementia medications in real-world clinical setting. The higher the initial severity of AD, the higher the cognitive decline rate.
ABSTRACT
Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.
ABSTRACT
Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support in vitro and in vivo studies. A quadratic regression (weighted 1/concentration2), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range from 9.05 to 6,600 ng/mL for carisbamate in rat plasma. Preclinical in vitro and in vivo studies of carisbamate have been studied through the developed bioanalytical method. Based on these study results, human pharmacokinetic (PK) profile has been predicted using physiologically based pharmacokinetic (PBPK) modeling. The PBPK model was optimized and validated by using the in vitro and in vivo data. The human PK of carisbamate after oral dosing of 750 mg was simulated by using this validated PBPK model. The human PK parameters and profiles predicted from the validated PBPK model were similar to the clinical data. This PBPK model developed from the preclinical data for carisbamate would be useful for predicting the PK of carisbamate in various clinical settings.