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S W Boellner

Publications and source records attributed to S W Boellner.

8 recordsLinked to original sources
PubMed2001

Single-dose gabapentin pharmacokinetics and safety in healthy infants and children.

Gabapentin (Neurontin) is a gamma-aminobutyric acid analogue indicated in adults for adjunctive treatment of partial seizures with or without secondary generalization. Two studies were conducted to determine the single-dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients. Forty-eight subjects were given single oral doses of gabapentin (10 mg/kg) while fasting. Enrollment was homogeneously distributed throughout the age range. Plasma samples were drawn predose and then serially for 24 hours postdose. Single doses of gabapentin were well tolerated by healthy pediatric subjects. Plots of pharmacokinetic parameters versus age suggested significant differences between younger (1 month to < 5 years) and older (> or =5 to 12 years) subjects. Mean area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 25.6 microg x h/mL in younger subjects and 36.0 microg x h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (Cmax) were 3.74 and 4.52 microg/ml (p < 0.05). Oral clearance (normalized for body weight) was 7.40 and 4.41 mL/min/kg in younger subjects and older subjects, respectively (p < 0.001). It was concluded that children between 1 month and < 5 years of age require approximately 30% higher daily doses of gabapentin than those > or =5 to 12 years of age.

Acetates↗
PubMed1998

Lack of pharmacokinetic drug interactions between tiagabine and carbamazepine or phenytoin.

Two single-center, open-label studies examined the potential effects of tiagabine on the pharmacokinetics and safety of carbamazepine and phenytoin at steady state. Twelve adult patients with seizures controlled by an individualized fixed dosage of antiepilepsy medication (carbamazepine or phenytoin) participated in each study. On day 1, the pharmacokinetics of the baseline antiepilepsy drug were determined. On days 2 through 18, tiagabine was titrated from 8 to 48 mg/d (or the maximum tolerated dose up to 48 mg/d), and the usual fixed dosage of carbamazepine or phenytoin was continued. The pharmacokinetic assessment was repeated on day 18. There were no statistically significant differences in carbamazepine, carbamazepine epoxide, and phenytoin pharmacokinetic parameters when either drug was administered alone or in combination with tiagabine. In each study, 11 of 12 patients (92%) experienced treatment-emergent adverse events after tiagabine was added. The most frequent adverse events were dizziness, headache, difficulty concentrating, drowsiness, and tremor. Most symptoms were mild or moderate in severity and resolved without further treatment, although tiagabine dosage reductions were required by 4 patients in the carbamazepine study and by 3 patients in the phenytoin study. There were no clinically important effects on physical examination or neurologic test results, laboratory values, or vital signs. The results suggest that addition of tiagabine to a fixed regimen of either carbamazepine or phenytoin is generally well tolerated and that carbamazepine and phenytoin steady-state pharmacokinetics are unaffected by the addition of tiagabine.

Adolescent↗
PubMed1998

Lack of a clinically significant pharmacokinetic drug interaction between tiagabine and valproate.

This single-center, open-label study examined the safety and potential effect of tiagabine on valproate pharmacokinetics under steady-state conditions. Twelve adult patients with seizures controlled by an individualized fixed dosage of valproate participated in the study. On day 1, the pharmacokinetics of valproic acid were determined. On days 2 through 14, tiagabine was titrated from 8 to 24 mg/d (or the maximum tolerated dose up to 24 mg/d), and the patients continued to take their usual fixed dosage of valproate. Valproic acid pharmacokinetics were assessed again on day 14. The mean maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve from time zero to the end of the dosing interval (AUC0-tau ) for valproic acid were reduced approximately 10% and 12%, respectively (p < or = 0.05), when valproate and tiagabine were administered concomitantly, compared with the mean values when valproate was administered alone. The concomitant administration of these drugs was generally well tolerated. Ten patients reported treatment-emergent adverse events during the study, the most common of which was dizziness(n = 8). Only one patient experienced events that were considered to be severe. There were no clinically important effects on laboratory values, vital signs, or physical exam findings. The small decreases in mean valproic acid Cmax and AUC0-tau observed during the concomitant administration of tiagabine and valproate are probably of limited clinical importance, given the broad therapeutic range of valproate (50-100 microg/mL).

Adolescent↗
PubMed1997

A single-dose study to define tiagabine pharmacokinetics in pediatric patients with complex partial seizures.

We report an open-label study of 25 children with complex partial seizures that assessed the pharmacokinetics and safety of a single dose of approximately 0.1 mg/kg tiagabine. The children received their usual individualized regimen of one concomitant antiepilepsy drug (AED) throughout the study. Seventeen children were receiving an inducing AED (carbamazepine or phenytoin); eight were receiving valproate. Tiagabine was well tolerated. Dose-normalized Cmax was higher in children taking valproate (18.2 +/- 5.0 ng/mL/mg) than in the induced children (14.8 +/- 6.9 ng/mL/mg), but the difference was not statistically significant. Dose-normalized area under the plasma concentration-time curve from time zero to infinite time was significantly higher (p = 0.002) in children taking valproate (176.5 +/- 54.7 ng.hr/mL/mg) than in induced children (92.4 +/- 56.7 ng.hr/mL/mg). Similarly, oral clearance in the children taking valproate (96 +/- 39 mL/min) was half that of the induced children (207 +/- 91 mL/min). Half-life in children taking valproate (5.7 hr) was almost twice that for the induced children (3.2 hr), and the elimination rate constant was significantly lower (p < 0.02) for the children taking valproate than for the induced children. Volume of distribution was similar in the children taking valproate (52 +/- 9 L) and the induced children (59 +/- 29 L). This is consistent with observations in adults taking tiagabine with inducing AEDs or valproate. Exploratory regressions on these data in children and previous data in adults showed fairly strong relationships between body size and tiagabine clearance and volume of distribution, with body size explaining about 40 to 50% of the variability. When adjusted per kg body weight, clearance and volume were greater in children than adults. When adjusted per m2 body surface area, clearance and volume were more similar in adults and children.

Anticonvulsants↗