Pharmacokinetic comparison of two valproic acid formulations: a plain and a controlled release enteric-coated tablets

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of Cognitive Evoked Potentials with Memory Tests in Patients with Memory Disturbance

We performed 3 kinds of memory tests and cognitive evoked potential study, P300, in 13 patients with memory disturbance and 19 control free of neurologic symptoms or history of neurological impairment; to determine correlation of each memory test with P300 and possibility of clinical application of P300 as a quantitative test of cognitive function. Patients and control younger than 40 years of age were selected to minimize the aging effect on the cognitive function tests. Those who marked 30 points in Mini-mental state examination were chosen as control. 11 of 13 patients had brrain lesions including temporal lobe. Comparing with tests in control group, the declarative ant the procedural memory of patients were significantly impaired (p<0.05, p<0.025, respectively), and P300 latency was significantly prolonged (p<0.001). In control group, among declarative memory tests Rey-Osterreith complex figure test and enhanced cued recall had significant correlation with P300 latency (p<0.05, p<0.05, respectively), while the Tower of Toronto test which was known to evaluate precedural memory did not. In patient group there was no significant correlation between any kind of memory test and P300 latency. These results not only are consistent with previous studies which detected temporal lobe as the origin of P300 wave, but implicate that brain loci other than temporal lobe might originate P300 wave. To apply P300 as a quantitative test of cognitive function, further extensive studies using age and IQ matched control will be needed.