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.

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.

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.

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.