P31 No interaction between doxapram and caffeine for the treatment of preterm neonates with apnea

Background In preterm neonates with apneas, co-administration with doxapram is often initiated in case of inadequate response to caffeine alone. While doxapram is exclusively registered for adults, there is limited information on its use in preterm infants. To examine whether the observed effects of doxapram are actually due to doxapram itself, and not a pharmacokinetic interaction between both respiratory stimulants, we studied the pharmacokinetics (PK) of caffeine in a population of preterm neonates receiving both caffeine and doxapram. Methods Caffeine concentrations from patients in the DINO study (NCT02421068) who received both caffeine and doxapram were analyzed using NONMEM V7.3. A PK model of caffeine in preterm neonates was used as a basis to estimate the PK parameters of caffeine when co-administered with doxapram with F fixed to 1 and k a fixed to 1.48 h -1 . 1 The results of the current study were compared to those of the reference population published by Charles et al. 1 Results In 15 preterm infants 58 samples were collected in which caffeine plasma levels were determined. Median gestational age (GA) was 26.3 (range 24–28) weeks, postnatal age (PNA) was 25 (0–63) days and current weight was 1100 (600–2140) grams. Caffeine CL and V d for an individual with a PNA of 12 days were estimated 0.2 L/h/70kg (RSE 28%) and 68.2 L/70kg (RSE 73%), respectively. Maturation of CL was best described by a power function with an exponent of 0.404 (RSE 89%). These results seem in good agreement with the reference population of preterm neonates receiving caffeine without doxapram with values of 0.167 L/kg/70 kg, 58.6 L/70kg and 0.358. 1 Conclusion In this pharmacokinetic study in preterm neonates receiving both caffeine and doxapram, we found similar values for CL, V d and maturation of CL with PNA compared to literature values obtained in preterm neonates receiving caffeine alone. References BG C. et al. Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther. Drug Monit 2008;30:709–716. Disclosure(s) Nothing to disclose