Plasma gabapentin concentrations in children with epilepsy: influence of age, relationship with dosage, and preliminary observations on correlation with clinical response.

The influence of age and administered daily dosage on the plasma concentrations of gabapentin (GBP) at steady state was evaluated in a group of 41 children and young adults (aged 3-30 years) receiving long-term adjunctive treatment with GBP for the management of refractory partial-onset seizures. For each patient, peak and trough concentrations were determined by a specific high-performance liquid chromatography (HPLC) method in samples obtained before the morning dose and 2.5 hours later, respectively. To assess within-subject relationship between plasma concentration and dosage, 30 patients were evaluated at more than one dosage level. Within the assessed dose range, plasma GBP concentrations were linearly related to dose. Apparent oral clearance values (mean +/- SD) in children aged 6 years or less (4.8 +/- 0.9 mL/kg/min) were comparable with those observed in children aged 7 to 15 years (4.6 + 1.5 mL/kg/min) and moderately higher than those found in young adults (3.9 + 0.9 mL/kg/min), even though differences among groups failed to reach statistical significance. There was, however, a significant difference in CL/F between children aged 10 years or less and older children (5.1 +/- 1.1 vs. 3.8 +/- 1.2 mL/kg/min, P < 0.005). Of the 41 patients who entered the study, 22 discontinued treatment, mostly due to insufficient efficacy. No significant difference in plasma GBP concentration was detected between patients showing a greater than 50% reduction in seizure frequency (4.1 +/- 1.9 microg/mL, n = 11, mean +/- SD) and those having no significant clinical improvement (4.4 +/- 1.7 microg/mL, n = 30). These results indicate that in children given dosages up to 50 mg/kg/d (mean, 25 mg/kg/d), GBP pharmacokinetic analyses show no important deviation from linearity. The data also suggest that, on average, children may need moderately higher dosages to reach plasma GBP concentrations comparable with those found in adults. There seems to be a large variation in the plasma concentrations of the drug associated with a favorable therapeutic response.

Improved enantioselective assay for the determination of fluoxetine and norfluoxetine enantiomers in human plasma by liquid chromatography.

A simple and innovative assay is described which allows the chiral separation of the four enantiomers of fluoxetine and norfluoxetine, with performance characteristics adequate for therapeutic drug monitoring. The assay requires liquid-liquid extraction into acetonitrile/n-hexane/isopropylic alcohol and re-extraction into phosphoric acid for clean-up. The acidic layer is injected onto the HPLC system after filtering. Separation of the analytes is achieved with a Chiralcel ODR column and a mobile phase consisting of potassium hexafluorophosphate/acetonitrile. Detection is made by ultraviolet absorbance at 227 nm. Standard curves are linear for each enantiomer (r(2)>/=0.992) over the range of 10-1000 ng/ml with a limit of quantification of 10 ng/ml for each enantiomer. Within-day and between-day CV% are