Biomedical subjects

G Oteri

Publications and source records attributed to G Oteri.

40 records · Page 3Linked to original sources

PubMedDate not supplied

Interaction of carbamazepine-10,11-epoxide, an active metabolite of carbamazepine, with valproate: a pharmacokinetic study.

The mechanism responsible for the valproate (VPA)-induced elevation of serum carbamazepine-10,11-epoxide (CBZ-E) levels was investigated in 6 normal subjects who received single oral doses of CBZ-E (100 mg) in a control session and during concurrent treatment with sodium VPA [500 mg twice daily (b.i.d.)]. VPA caused a significant prolongation of CBZ-E terminal half-life (t1/2 from 6.3 +/- 1.2 to 9.0 +/- 2.0 h, mean values +/- SD) and decreased CBZ-E clearance (from 90.6 +/- 18.8 to 63.2 +/- 16.1 ml h-1 kg-1, mean values +/- SD) without affecting CBZ-E apparent volume of distribution (from 0.82 +/- 0.19 to 0.81 +/- 0.24 l kg-1, mean values +/- SD). These findings indicate that VPA impairs the elimination of CBZ-E, presumably by inhibiting its metabolism.

Absorption↗

PubMedDate not supplied

Carbamazepine-valnoctamide interaction in epileptic patients: in vitro/in vivo correlation.

Six patients stabilized with carbamazepine (CBZ) therapy received an 8-day "add-on" supplement of valnoctamide (VCD), a tranquilizer available over the counter (OTC) in several European countries that exhibits promising anticonvulsant activity in animal models. During VCD intake, serum levels of the active CBZ metabolite, carbamazepine-10,11-epoxide (CBZ-E), increased fivefold from 1.5 +/- 0.7 micrograms/ml at baseline to 7.4 +/- 4.4 micrograms/ml after 4 days of VCD therapy and 7.7 +/- 3.1 micrograms/ml after 7 days of VCD therapy (means +/- SD, p < 0.01). In 4 patients, the increase in serum CBZ-E levels was associated with clinical signs of CBZ intoxication. CBZ-E levels returned to baseline after VCD therapy was discontinued. Serum CBZ levels remained stable throughout the study. The interaction observed in this study is similar to that described in patients treated with CBZ and valpromide (VPD, an isomer of VCD). In a mechanistic study, therapeutic concentrations of VCD inhibited hydrolysis of styrene oxide in human liver microsome preparations. Thus, VCD is a potent inhibitor of microsomal epoxide hydrolase (IC50 15 microM). There was a striking similarity between in vitro and in vivo inhibition potencies. In this study, VCD clearance was higher in epileptic patients (treated with CBZ) than in healthy subjects.

Adult↗

PubMedDate not supplied

[Lennox-Gestaut syndrome: therapeutic aspects].

The Lennox-Gastaut Syndrome is one of the most refractory form of epilepsy and a variety of compounds, such as traditional antiepileptics, "new anticonvulsants" and non-anticonvulsant drugs has been tested. ACTH and, among the traditional antiepileptics. Clonazepam and Sodium Valproate showed the most favorable effects. The immediate (within 6 months) therapeutic response to ACTH and Clonazepam is satisfactory, with a more than 50% reduction of seizures in about one half of patients; after one year, however, only a small percentage of cases (7-10%), rather close to that with spontaneous remission, shows some therapeutic benefit. Valproate, when used as a single drug, produces a decrease in seizures (greater than 50%) in 25-30% of pts. A list of compounds, such as amphetamine, taurine, amantadine, allopurinol and, among the new putative antiepileptics, cinromide and gamma-vinyl-GABA, has been tested with some occasionally observed improvement in seizure control. None of these compounds, however, is of really proven efficacy. An acquired general rule of treatment is to avoid complex polypharmacy and overdose; there is in fact good evidence that making the child drowsy will greatly increase the number of fits.

Anticonvulsants↗

PubMedDate not supplied

[Recessive hereditary ataxia with early onset. Clinical study of 27 cases].

Twenty-seven patients with autosomal recessive ataxia were studied. According to diagnostic criteria proposed by Quebec Cooperative Study, fifteen cases were diagnosed as Friedreich's ataxia. The remaining twelve cases showed clinical features of the "Early onset cerebellar ataxia with retained reflexes". The clinical differences between the two diseases are discussed. The high percentage of patients with "early onset cerebellar ataxia" is underlined.

Adolescent↗