Determination of theophylline clearance in South African children.

Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability. Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l.h-1.kg-1 were 0.0949 for children aged 1-5 y; 0.0813 for children aged 5-9 y, and 0.0660 for children of 9-16 y. The values are similar to those reported in other studies.

Pharmacokinetic consultation program in a pediatric asthma clinic.

The effect of a clinical pharmacokinetic consultation program for theophylline on the outcomes of pediatric patients with asthma was studied. The program was established in 1989 at a pediatric asthma clinic. For each patient visit, a clinical pharmacist recorded demographic, clinical, and medication-related information and counseled the parents. When an adjustment in the theophylline dosage was indicated, the pharmacist calculated the appropriate dosage using population pharmacokinetic values. If the pediatrician requested a measurement of the serum theophylline concentration, the time when the blood sample was drawn relative to the last dose was recorded, an average serum theophylline concentration at steady state and individualized pharmacokinetic values were calculated, and the dosage was adjusted accordingly. Patient data were compared among three stages: (1) the month before and the month of entry into the program, (2) months 5 and 6 after entry, and (3) months 11 and 12 after entry. A total of 44 patients were studied during each of stages 1 and 2, and 29 patients were reviewed during stage 3. There was a significant improvement in wheezing from stage 1 to stage 2 and in exercise tolerance and nocturnal coughing from stage 1 to stage 2 and stage 1 to stage 3. Forced expiratory volume in one second improved significantly from stage 1 to stage 2, and there was a significant reduction in the necessity for hospital visits for the treatment of exacerbations of asthma between stages 1 and 2. The daily weight-adjusted dose of theophylline increased significantly after the program began. Asthmatic children taking theophylline had improvements in outcome variables after pharmacokinetic consultation and medication counseling were initiated.