Severe side effects and drug plasma concentrations in preterm infants treated with doxapram

A high-performance liquid chromatography method has been developed for simu ltaneous determination of doxapram and its metabolites including keto-doxap ram, the main and only active metabolite. The aim of the study was to evalu ate this microtechnique and to report the cases involving severe adverse ef fects to determine toxic plasma levels in neonates. The method was found to be selective, and showed a good baseline separation of doxapram and metabo lites. Recovery, linearity, intraday/interday precision, and limit of detec tion determined in aqueous solutions and in spiked plasma were satisfactory . The assay is simple, rapid, and plasma-sparing, which represents a true a dvantage in managing neonates. Case analysis was performed in two consecuti ve periods: 124 preterm infants in the first period and 173 in the second p eriod. Severe toxic effects were observed in 4 cases in the first period, w ith doxapram plus keto-doxapram levels 9 mg/L. In the second period, only o ne case was observed. High-range plasma concentrations were significantly l ess frequent in the second period than in the first one. The authors conclu de that measuring doxapram plus keto-doxapram in plasma may be of interest to avoid severe toxic effects in preterm neonates treated with doxapram.