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Biomedical subjects

G Oteri

Publications and source records attributed to G Oteri.

At least 37 records · Page 2Linked to original sources
PubMed1986

Carbamazepine-viloxazine interaction in patients with epilepsy.

In six depressed epileptic patients stabilised on carbamazepine therapy, addition of the antidepressant agent viloxazine (300 mg/day for three weeks) induced a marked (average 55%) increase in steady-state plasma carbamazepine concentration. The concentration of the active metabolite carbamazepine-10,11-epoxide also increased during viloxazine therapy, but to a lesser extent (16%). In three patients, these effects were associated with symptoms of carbamazepine intoxication, which regressed rapidly when plasma carbamazepine and carbamazepine-10,11-epoxide levels returned to baseline values after discontinuation of viloxazine. In a seventh patient, viloxazine had to be discontinued after only two weeks because of severe side effects associated with a striking elevation of carbamazepine and carbamazepine 10,11-epoxide levels (by 197% and 137% respectively). Although viloxazine appears to be one of the few antidepressants which can be used safely in patients with epilepsy these results indicate that the drug should be prescribed with great caution in subjects treated with carbamazepine. The mechanism of the interaction probably involves inhibition of the metabolism of both carbamazepine and its active epoxide metabolite.

Adult↗
PubMed1984

Single-dose kinetics of primidone in acute viral hepatitis.

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.

Acute Disease↗
PubMed1984

A sensitive gas chromatographic assay for the determination of serum viloxazine concentration using a nitrogen-phosphorus-selective detector.

A gas-liquid chromatographic procedure for measuring the serum levels of the antidepressant viloxazine is described. The drug and the internal standard [imipramine (IMI)] are extracted from 1 ml serum. The method involves a three-step extraction, derivatization of viloxazine with acetic anhydride, and injection into a gas chromatograph equipped with a nitrogen-phosphorus-selective detector. The retention times for IMI and viloxazine were 4.7 and 6.1 min, respectively. The standard curves were linear over the 100- to 2,000-ng/ml range. The recovery averaged 64.5% and the lowest detection limit was 80 ng/ml. The within-run and day-to-day coefficients of variations were 11.9 and 12.5%, respectively, at 250 ng/ml, and 8.9 and 9.2%, respectively, at 1,500 ng/ml. The method is adequate both for single-dose pharmacokinetic studies and for monitoring serum viloxazine levels in chronically treated patients.

Adult↗
PubMed1984

Effect of viloxazine on serum carbamazepine levels in epileptic patients.

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.

Adult↗
PubMed1984

Valproic acid-ethosuximide interaction: a pharmacokinetic study.

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.

Adolescent↗
PubMed1983

Intra-daily oscillations in dipropylacetic acid plasma levels with two or three daily doses of dipropylacetamide in epileptic patients.

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.

Adolescent↗
PubMed1983

Effects of steroid hormones on muscle reinnervation after nerve crush in rabbit.

The ability of an association of three steroid hormones to influence the reinnervation process and the trophism of rabbit muscles denervated by crush of the sciatic nerve was investigated. The beginning of reinnervation was established with electromyographic recordings from the tibialis anterior muscle. The distance from the site of crushing to the point where the motor nerve enters the tibialis anterior muscle was then measured in each animal, and the nerve regeneration velocity (mm/day) was calculated: a slightly but significantly higher (P less than 0.001) mean value was found in treated animals compared with untreated ones. When soleus and extensor digitorum longus (EDL) muscles were histochemically examined 50 days after lesion, a larger mean diameter of type 2c fibers was found in treated than in untreated animals, pointing out a possible useful effect of the treatment. On the contrary, the size reduction of EDL type 2b fibers was more pronounced in treated rabbits, indicating a catabolic influence of the drugs on this fiber type.

Animals↗
PubMed1982

Increased dipropylacetic acid bioavailability from dipropylacetamide by food.

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.

Absorption↗
PubMed1981

Dipropylacetic acid plasma levels; diurnal fluctuations during chronic treatment with dipropylacetamide.

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.

Adolescent↗
PubMed1980

Preliminary data on dipropylacetamide absorption in rats.

Absorption of dipropylacetamide, after oral and i.m. administration, was studied in different groups of male albino Wistar rats. After i.m. administration, only unmodified amide was found in plasma, whereas oral administration of the drug was followed by the presence of dipropylacetic acid and dipropylacetamide in plasma. This last compound resulted in a higher amount in a further group of rats previously treated with neomycin in order to avoid the action of intestinal flora. Present results seem to exclude an hepatic role in the transformation of dipropylacetamide in dipropylacetic acid.

Absorption↗
PubMedDate not supplied

Sodium valproate and valpromide: differential interactions with carbamazepine in epileptic patients.

To evaluate the comparative effects of valproic acid (VPA) and valpromide (VPM) on plasma levels and protein binding of carbamazepine (CBZ) and CBZ-10,11-epoxide (CBZ-E), 12 adult epileptic patients stabilized on CBZ monotherapy were divided into two groups. One group (n = 6) received sodium valproate (1,100 mg/day) for 2 weeks, while the other group (n = 6) was given, for the same period, a dosage of VPM (1,200 mg/day) expected to produce VPA levels equivalent to those achieved with valproate. Plasma CBZ levels were not affected by either treatment. In the valproate-treated group, plasma CBZ-E levels increased by 101% (range, 29-238%) within 1 week of combined therapy (p less than 0.02) and returned to baseline values after VPA treatment was stopped. In the VPM-treated patients, the elevation of plasma CBZ-E levels was much greater. In this group, plasma CBZ-E increased by 330% (range, 110-864%), and this was associated in two patients with the appearance of adverse effects which subsided after reducing the VPM dosage. The plasma protein binding of CBZ and CBZ-E was not affected significantly by VPM or valproate therapy. Plasma VPA levels were similar in the two groups. It is concluded that VPM is not simply a prodrug of VPA. Although both VPA and VPM increase CBZ-E levels--probably by inhibiting the enzyme epoxide hydrolase--the interaction caused by VPM is of much greater magnitude and potential clinical significance.

Carbamazepine↗