Optimization of theophylline dosage regimen in preterm infants based on drug serum level during non-steady state

Abstract

The study was performed in thirty-three preterm infants admitted at Queen Sirikit National Institute of Child Health to evaluate the reliability and precision of the predicted steady state theophylline serum concentration based on the non-steady state serum concentration, the appropriateness of the loading dose and the correlation between the drug concentration and clinical response. Theophylline dosage regimen used in this study was a present dosage regimen used at the institute. Theophylline serum concentrations of majority patients were less than therapeutic range at 6 hours after administered 5.63±0.86 mg/kg of loading dose. From this study, the suggested aminophylline loading dose should be 6.5 mg/kg for the patients used the drug during the first week of life and 7.0 mg/kg for the patients used the drug during the second weeks of life and the maintenance dose could be calculated by using the equation MD(mg/kg/day) = 3.50+(0.91xPNA in wks). Pharmacokinetic parameters were used to predict the steady state serum concentration. These parameters were either calculated individually from the non-steady state theophylline serum concentration or obtained as the reported population values. All methods had reliability but lacked of precision in prediction of the steady state serum concentrations (α = 0.05). Among the different methods, the method which used the individual Ke calculated from the non-steady serum concentration and the population Vd (0.858L/kg) applied to the simplified equation resulted in best prediction of the steady state serum concentration. เท clinical practice, this method might be a choice for calculation of the maintenance dose in preterm infants before the steady state serum concentration was reached. Theophylline serum concentration was correlated to clinical response, most patients had benefit effect when the drug concentration was within therapeutic range. The traditional maintenance doses of eight patients were adjusted before the steady state serum concentration was reached. The clinical response was improved after adjustment of the maintenance dose in most of these patients. However, the benefit effect was often obtained when other treatments were used along with the drug, especially when the drug concentration was in subtherapeutic range. Higher incidence of adverse reaction was found when the drug concentration was higher than the therapeutic range. The only one type of adverse reaction found in this study was tachycardia with the heart rate higher than 180 beats per minute.