Variations in carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-EP) concentrations were measured in saliva over 24 hours in 33 children with complex partial seizures and/or generalized tonic-clonic seizures; all patients received CBZ as monotherapy. CBZ varied between 37-104% and CBZ-EP varied between 26-119%. One venous blood sample was obtained simultaneously with the first saliva sample before the morning dose of CBZ. The free fraction of plasma CBZ was 25.5%. Medication side effects are most likely to appear within 3-4 hours of drug intake; therefore, it is advisable to take another sample in children demonstrating time-related side effects. A controlled release formulation of CBZ should minimize the fluctuations of salivary drug levels of CBZ and CBZ-EP.

Adolescent↗

PubMedDate not supplied

Tissue disposition of glyceryl trinitrate, 1,2-glyceryl dinitrate, and 1,3-glyceryl dinitrate in tolerant and nontolerant rats.

The tissue distribution of glyceryl trinitrate (GTN) and its two dinitrate metabolites 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl trinitrate (1,3-GDN), was studied in GTN-tolerant and nontolerant male Sprague-Dawley rats. The concentrations of GTN, 1,2-GDN, and 1,3-GDN were measured in plasma, heart, brain, liver, aortic tissue, and adipose tissue at various time points after a subcutaneous dose of GTN (50 mg/kg). At the first time point (5 hr), concentrations of GTN, 1,2-GDN, and 1,3-GDN in plasma were equal for tolerant and nontolerant rats, but the elimination rate was altered for the tolerant rats as compared with nontolerant rats. In adipose tissue, the concentration of GTN was significantly higher as compared with concentrations of the dinitrate metabolites. In contrast, the other tissues studied showed significantly higher concentrations of the GDNs when compared with GTN. The 1,3-GDN/1,2-GDN ratio decreased with time for both tolerant and nontolerant rats. This study indicates that long-term GTN administration results not only in tolerance development, but also in altered pharmacokinetics of GTN, 1,2-GDN, and 1,3-GDN. The results also show that the 1,3-GDN/1,2-GDN ratio is dependent on the GTN concentration.

Animals↗