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Biomedical subjects

E Perucca

Publications and source records attributed to E Perucca.

At least 145 records · Page 8Linked to original sources
PubMed1990

Pharmacokinetics of a valpromide isomer, valnoctamide, in healthy subjects.

The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a pro-drug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.

Adult↗
PubMed1990

Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis.

The long-term efficacy of primidone (375-750 mg/day) in essential tremor was evaluated prospectively in 11 patients who had shown a favorable response to 4-week treatment with the drug under placebo-controlled conditions. On accelerometric evaluation, the magnitude of tremor after 3, 6, and 12 months on primidone was still significantly reduced compared with the initial placebo period. After discontinuation of primidone, tremor amplitude reverted to the placebo levels. Some loss of efficacy during long-term administration, however, was suggested by the results of self-assessment, physician's assessment, and performance tests. Three patients discontinued prematurely the drug because the sedative effects outweighed the potential therapeutic benefit. Side effects (especially drowsiness and sedation) were common at 4 weeks and 3 months but tended to subside thereafter. It is concluded that primidone retains at least part of its tremorolytic effect for up to 1 year, although the overall clinical benefit is limited in most patients.

Aged↗
PubMed1990

The disposition of primidone in elderly patients.

1. The pharmacokinetics and metabolism of primidone at steady-state were studied in 10 elderly patients aged 70-81 years and eight control subjects aged 18-26 years. 2. Primidone half-lives and clearance values (mean +/- s.d.) were similar in the elderly and in the young (12.1 +/- 4.6 vs 14.7 +/- 3.5 h and 34.8 +/- 9.0 vs 33.2 +/- 7.2 ml h-1 kg-1 respectively. 3. The serum concentrations of the metabolites phenylethylmalonamide (PEMA) and phenobarbitone relative to those of parent drug were higher in the elderly than in the young, the difference being significant (P less than 0.01) in the case of PEMA. 4. The renal clearances of primidone, phenobarbitone and PEMA were moderately decreased in the elderly but this reduction was statistically significant only for PEMA. Elderly patients excreted a reduced proportion of unchanged primidone and an increased proportion of PEMA in urine. 5. Ageing is associated with a greater accumulation of PEMA, which is unlikely to have a major clinical significance.

Adolescent↗
PubMed1989

Impaired bioavailability of famotidine given concurrently with a potent antacid.

The effect of a high potency antacid on the oral bioavailability of a single dose of famotidine (40 mg) was evaluated in normal volunteers according to a randomized cross-over design. Ingestion of the antacid concurrently with famotidine resulted in a significant reduction of peak plasma famotidine concentration (from 156 +/- 22 to 104 +/- 7, P less than 0.05) and area under the famotidine plasma concentration curve (from 956 +/- 125 to 607 +/- 56, P less than 0.02). No significant interaction was observed when the antacid was ingested 2 hours after famotidine administration.

Administration, Oral↗
PubMed1989

Time-dependent pharmacodynamic effects of phenobarbital in humans.

The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design. Compared with the placebo session, phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF), whereas no significant effects were detected on choice reaction times, tappings, and digit symbol substitutions. There was a clear-cut dissociation between the time course of serum phenobarbital levels, which remained at a plateau throughout most of the period of observation (up to 72 h) and its subjective (VARS) and objective (CFF) effects, which could be documented only for up to 9 h after administration. These data suggest that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. Multiple Sleep Latency Tests (MSLTs) were also performed in the same subjects and showed that phenobarbital increases diurnal drowsiness and attenuates the circadian variation in drowsy state that is seen under control conditions. MLSTs appeared to be superior to other tests in documenting the sedative effects of the barbiturate.

Adult↗
PubMed1989

Effects of vigabatrin on evoked potentials in epileptic patients.

1. Somatosensory (SEP) brainstem auditory (BAEP) and visual (VEP) evoked potentials were determined before and after add-on administration of vigabatrin (GVG) in patients with epilepsy. 2. At pre-treatment assessment SEP and BAEP parameters were usually found to be within normal limits, while P100 latencies of the VEP were abnormally prolonged in a considerable proportion of patients. 3. In a double-blind, placebo-controlled trial in 22 patients GVG (1-3 g day-1 stratified according to body weight) given for 7 weeks did not modify any of the evoked potential parameters evaluated. 4. Eighteen patients were evaluated prospectively at regular intervals during long-term GVG (2-4 g day-1) therapy with a mean follow up of 24 months (range 13-42 months). SEP, BAEP and especially VEP parameters showed some interindividual variability, but the within patient variation was relatively small. No consistent important changes were seen in association with GVG, although a possible trend towards a shortening of BAEP latencies and P100 latencies was observed. 5. The relevance of these findings with respect to GVG safety is discussed.

Adolescent↗
PubMed1989

Pharmacokinetics of dextromoramide in surgical patients.

The pharmacokinetics of the narcotic analgesic dextromoramide was investigated by means of a specific GC-MS method in 9 patients who were given a single oral dose of the drug (7.5 mg) together with an anticholinergic before undergoing minor orthopedic surgery. Dextromoramide was rapidly absorbed from the gastrointestinal tract, with peak plasma levels between 68 and 177 micrograms/L usually achieved within 0.5-4.0 h after dosing. In 5 patients, the decline of plasma concentrations after the peak followed a biphasic pattern, with half-lives of 0.4-1.6 h for the first phase and 6.3-21.8 h for the terminal phase. In the remaining patients, no clear-cut biphasic pattern was seen and half-lives calculated over the period between 4 h and 10 h after administration ranged from 1.5 to 4.7 h. Apparent clearance and volume of distribution values ranged from 0.06 to 0.36 1.h-1.kg-1 and from 0.6 to 2.4 l.kg-1, respectively. Less than 0.06% of the dose was excreted unchanged in urine within 8 h of administration. The concentration of the drug in a CSF sample collected 1 h after dosing was below the limit of detection (2 micrograms/L) in all subjects.

Adolescent↗
PubMed1989

Vigabatrin in the treatment of epilepsy: a long-term follow-up study.

Twenty-five adult epileptic patients who had shown a satisfactory clinical response to add-on vigabatrin under placebo-controlled conditions continued on long-term treatment for up to 47 months (median 22 months). The initially favourable therapeutic response was generally maintained throughout the observation period with an overall good clinical tolerance. No evidence of neurotoxicity was detected by multimodal evoked potentials monitoring.

Adult↗
PubMed1989

[Obstetric and perinatal management of myasthenia gravis].

Three new cases of patients with myasthenia gravis during pregnancy are presented. The unpredictable course of myasthenia gravis (MG) in pregnancy is discussed. The course of labor in patients with MG is normal. The effects of certain drugs on the course of diseases are assessed. In our group of patients only one patient had an exacerbation of her MG after using an aminoglycoside. There were 7 live births. None of the newborns developed neonatal myasthenia.

Adult↗
PubMed1989

[Gestation of 42 weeks or longer. Management protocol].

We have evaluated, in a prospective approach to the perinatal results of 98 patients with gestation of 42 weeks and more. The patients with an uncertain gestation age were excluded. The vigilance of the fetus was realized by electronic monitorization, sonographic examination and amnioscopy 55.1% of patients begin labor spontaneously 44.9% were interrupted. The principals causes of interruption were pelvic score of bishop > 7 points and condition that suggest fetal injury. In 31.6% of patients a cesarean section was made. Neonatal morbidity was a 19.4% and we don't have mortality.

Adult↗
PubMed1989

Pharmacokinetics of salicylic acid following administration of aspirin tablets and three different forms of soluble aspirin in normal subjects.

The pharmacokinetic profile of an innovative formulation of soluble aspirin (l-ornithine acetylsalicylate, ldB 1003) was compared with that of conventional tablets and two other soluble dosage forms (d, l-lysine acetylsalicylate and a buffered effervescent formulation of acetylsalicylic acid) after administration of single oral doses in six normal volunteers. All soluble forms showed a rapid absorption profile, peak plasma salicylic acid levels being attained after about 30 min on average and without statistically significant differences among the solutions tested. As compared to the soluble formulations, acetylsalicylic acid given as tablets resulted in slower absorption, with peak plasma salicylic acid levels being reached more than 1 h after dosing. Despite these differences in time course of plasma level profiles, the extent of absorption was similar for all formulations. Apart from the potential advantages in terms of improved gastric tolerability, the increased rate of absorption of aspirin solutions is therapeutically useful whenever a rapid onset of action is required. In this respect, the kinetic pattern of the innovative formulation compares favourably with that of other available soluble dosage forms.

Adult↗
PubMed1988

Lack of effect of cholestyramine on phenytoin bioavailability.

The effect of cholestyramine (4 g qid for 5 days) on the kinetics of phenytoin (400 mg orally) was investigated in normal subjects. Apart from a trend toward faster phenytoin absorption, the serum level profile of the drug during concurrent cholestyramine coadministration was similar to that observed in a control session. Areas under the serum phenytoin concentration curves were virtually identical in the two occasions. It is concluded that cholestyramine does not significantly affect the bioavailability of a single dose of phenytoin.

Adult↗
PubMed1988

Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects.

The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3-hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin.

Adult↗
PubMed1988

Effect of valpromide on the pharmacokinetics of carbamazepine-10, 11-epoxide.

The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h and decreased CBZ-E clearance from 73.5 +/- 20.0 to 23.5 +/- 4.0 ml h-1 kg-1 (P less than 0.01). These results suggest that the elevation of plasma CBZ-E levels in patients receiving carbamazepine and VPM in combination is due to inhibition of epoxide hydrolase in the liver.

Adolescent↗
PubMed1988

Effect of vigabatrin (gamma-vinyl-GABA) on visual, brainstem auditory and somatosensory evoked potentials in epileptic patients.

Visual (V), somatosensory (S) and brainstem auditory (BA) evoked potentials (EPs) were determined in 22 epileptic patients, mostly with partial seizures, who received add-on treatment with vigabatrin (1-3 g/day, stratified according to body weight) and placebo, each given for 7 weeks according to a double-blind, randomized cross-over design. At pretreatment assessment, BAEPs and SEPs were found to be within normal limits in most of the patients tested, while for VEPs several abnormal responses were found, including a marked prolongation of P100 latency values in the majority of cases. None of the EP parameters examined was significantly influenced by vigabatrin treatment. These results support the evidence that enhancement of GABA-ergic transmission does not substantially affect the functional state of afferent sensory pathways as assessed by EP analysis. The significance of these findings with respect to the safety of vigabatrin therapy is discussed.

Adolescent↗
PubMed1988

Double-blind comparison of primidone and phenobarbital in essential tremor.

In a double-blind cross-over trial, primidone was superior to both placebo and phenobarbital in reducing essential tremor in 13 patients. Phenobarbital, at a dosage yielding serum barbiturate levels greater than those seen with primidone, was not better than placebo. Thus, primidone has an effect in essential tremor independent from that of its metabolite phenobarbital.

Clinical Trials as Topic↗