Biomedical subjects
Publications and source records attributed to R Di Perri.
The clinical, neuropathological and ultrastructural features of a case of Kufs disease (Meyer basal ganglia form) are reported. In the present case, besides the typical lesions of Neuronal Ceroid-Lipofuscinosis, and increased iron reaction at pallidonigral level was detected histochemically. The significance of the last finding is discussed.
The sleep pattern and conditions at the time of awakening were investigated by means of polygraphy and tests in 6 healthy adult volunteers following administration of amineptine. The drug was found to increase the number and duration of the REM phases, without affecting the overall sleeping time but reducing sleep latency. The tests carried out revealed a higher sensation of well-being, improved attention and concentration in the morning.
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The pharmacokinetics of primidone (PRM) after oral administration of a single 500 mg dose was studied in 7 patients with acute viral hepatitis and 7 healthy control subjects. The elimination half-life and the apparent clearance of unchanged PRM in the patients were 18.0 +/- 3.1 h and 42 +/- 14 ml X h-1 X kg-1, respectively (mean +/- SD) and did not differ significantly from the values in the controls (half-life 17.0 +/- 2.4 h; clearance 35 +/- 8 ml X h-1 X kg-1). The metabolite phenylethylmalonamide (PEMA) was detected in the serum of all normal subjects within 2-24 h. By contrast, serum levels of this metabolite were undetectable (less than 2 mumol/1) in all but one of the patients. Serum levels of phenobarbital (PB) remained below the limit of detection (less than 2 mumol/1) in all subjects. The findings indicate that accumulation of PRM with its attendant toxicity is unlikely to occur in epileptic patients who develop acute viral hepatitis, despite evidence that the metabolism of the drug is affected by this condition. The possibility of impaired conversion to PB and its implications are discussed.
The present study describes the interaction between carbamazepine (CBZ) and viloxazine, a recently synthesized antidepressant agent. Seven epileptic patients on chronic anticonvulsant therapy showed a significant (p less than 0.005) increase in steady-state serum CBZ levels (from 8.1 +/- 2.5 SD to 12.1 +/- 2.5 SD micrograms/ml) when viloxazine (300 mg/day) was added to the therapy. The effect was associated with the appearance of mild CBZ intoxication. The symptoms of this intoxication (i.e., dizziness, ataxia, fatigue, drowsiness) disappeared rapidly, and serum CBZ levels decreased to the basal values, when viloxazine administration was stopped.
The present pharmacokinetic study was designed to investigate the possible interaction between valproic acid (VPA) and ethosuximide (ESM) in humans. Six drug-free healthy volunteers, four men and two women, 18-42 years of age, received a single oral dose of 500 mg ESM before and during a treatment with VPA at 800- to 1,600-mg daily doses. The second ESM dose was given 9 days after VPA administration was started. In this latter condition, a significant (p less than 0.05) increase in ESM serum half-life, from 44 to 54 h on average, and a significant (p less than 0.05) decrease in total body clearance, from 11.2 to 9.5 ml/min on average, were observed. Other pharmacokinetic parameters were unchanged and showed values similar to those reported in the literature. Serum VPA levels ranged between 66.8 and 95 micrograms/ml. Two subjects showed no evidence of interaction. Although a great interindividual variability in the occurrence of VPA-ESM interaction can be observed, the present study indicates that VPA is able to inhibit the metabolism of ESM. Possible factors affecting this interaction are hypothesized and discussed.
The effects of non-convulsive doses of i.v. penicillin (1.100.000/1.300.000 I.U./Kg) on the ECoG of rabbits was studied. A tendency to an increase in spindling activity together with the presence of characteristic penicillin spikes, polyspikes and spike and wave complexes often preceding or intermixed to the spindling activity, was the most prominent finding. These data indicate that spindles and penicillin induced spikes show a straight correlation and seem consistent with the hypothesis that spindles have a facilitant effect on epileptic discharges.
The diurnal fluctuations in dipropylacetic acid (DPA) plasma levels were examined in ten epileptic patients following a chronic treatment with 3 or 2 daily doses of dipropylacetamide (DPM). The highest/lowest DPA levels ratios observed throughout 24 hrs were 1.18 and 1.36, respectively, but the difference in the data was not statistically significant (p greater than 0.05). The present results indicate that a reduction of the frequency of the daily administrations of the drug can be made with consequent possible improvement in the patient's compliance. The clinical value of the oscillations in DPA serum levels is also revised in the light of the data reported in the literature.
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The present study was designed to investigate the influence of food on dipropylacetic acid (DPA) absorption from dipropylacetamide (DPM). Six healthy male volunteers received at weekly intervals, in a crossover randomized fashion, a single oral dose of 60 mg DPM, as 2 X 300-mg capsules, in a fasting state and after a standard meal. In the latter state, the lag time of DPA appearance in the serum increased significantly (p less than 0.02) from 0.6 +/- 0.2 to 2.3 +/- 1.2 h (mean values +/- SD). Maximal DPA serum levels and bioavailability increased significantly (p less than 0.05), with mean values of 27.7 +/- 19.8 and 19.0 +/- 14.7%, respectively, following food. The slower gastric emptying with a consequent improved DPM exposure to metabolizing enzymes and changes in gastric pH probably accounted for these findings. These results suggest that it is more advantageous to take DPM after meals. This helps to reduce gastrointestinal disturbances and to promote DPA absorption.
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Diurnal variation in dipropylacetic acid (DPA) plasma levels was investigated in 47 and 42 epileptic patients, chronically treated with sodium dipropylacetate and dipropylacetamide (DPM), respectively, taken alone or in addition to other antiepilepic drugs. Fluctuation in DPA plasma levels was significantly less in patients receiving dipropylacetamide. The slow absorption and the more prolonged plasma half-life of dipropylacetamide accounted for these findings. Although the importance of diurnal fluctuations in DPA levels has not yet been established, possible clinical implications are discussed.
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