Background and aims Morphine is used in preterm infants, but data are scars on pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PG). We aimed to study PK and PD/PG relation of morphine in infants included in a RCT comparing morphine with short-acting analgosedation as premedication for intubation.
Methods 17 preterm infants with a median (IQR) gestational age of 26.6 (25.1–28.7) w, birth weight 924 (721–1240) g and postnatal age 136 (17.5–322) h were randomized to receive morphine (0.3 mg/kg).
Blood samples for morphine, M6G and M3G concentrations were collected before administration, 20 min, 6 and 24 h after intubation. DNA was isolated from salivary swabs to genotype 18 polymorphisms in 12 genes using Taqman assays. Pain assessment (ALPS-0 and EDIN scales) was performed and additional morphine boluses were offered accordingly. The morphine level/pain score relation and the genotype influence on time to achieve a low pain score was calculated.
Results In infants receiving no additional doses, clearance was 1.5–3.3 ml/kg/min in 5 infants of 5–34 h and 9.9 in one infant of 332 h postnatal age.
Both morphine and morphine+M6G/5 correlated with mean ALPS-0 score at 6h (p=0.02 and 0.04) and 24 h (p=0.01 and 0.02). The COMT rs4680G>A (Val158Met) SNP was significantly correlated with time to reach the lowest pain score. COMT rs4680A patients experienced a faster response to opioids compared to rs4680GG patients in both groups (p=0.001 and p=0.072).
Conclusions Morphine clearance is dependent on postnatal age in premature infants. Genotyping would improve individual dosing of opioids during NICU-care.