Population pharmacokinetic modelling of carbamazepine in epileptic elderly patients: implications for dosage.

BACKGROUND: Proper use of antiepileptic drugs in the elderly involves knowledge of their pharmacokinetics to ensure a patient-specific balance between efficacy and toxicity. However, populations of epileptic patients on chronic carbamazepine (CBZ) therapy which have been studied have included data of relatively few elderly patients. AIMS: The aim of the present study was to evaluate the population pharmacokinetics of CBZ in elderly patients on chronic monotherapy. METHODS: We have used the non-parametric expectation maximization (NPEM) program in the USC*PACK collection of PC programs to estimate individual and population post-induction pharmacokinetics of CBZ in epileptic elderly patients who received chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly and 35 younger patients with epilepsy. As a 'historical control' we used previously published population modelling results from 99 young epileptic patients on chronic CBZ monotherapy. In that control group, TDM was performed in the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in the present study, and the same PK population modelling software was used for data analysis. RESULTS AND CONCLUSIONS: A poor correlation was found between daily CBZ dose and serum concentrations in the elderly patients (r=0.2, P=0.25). Probably statistically significant difference in the median values of the CBZ metabolic rate constant (P<0.001) between elderly and relatively young epileptic patients was found. Our results showed that age-related influences in CBZ pharmacokinetics in elderly patients should be considered in the optimal planning of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ dosages lower than those based on the median population PK parameter values obtained from younger patients. The present population model is also uniquely well suited for the new 'multiple model' design of dosage regimens to hit target therapeutic goals with maximum precision.

A randomized comparison of triple therapy Helicobacter pylori eradication regimens in children with peptic ulcers.

An open, randomized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease. A total of 106 children (5 - 15 years) were treated for 1 week with metronidazole, 30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age; generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily. The H. pylori eradication rate was significantly higher in patients receiving proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%) or ranitidine (74.3%), and this was associated with a trend towards faster ulcer healing. It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H. pylori and ulcer healing in children with peptic ulcer disease, and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this study.