Losartan attenuates symptomatic and hormonal responses to hypoglycemia in humans

Abstract

Ibuprofen pharmacokinetics showed a large interindividual variation in premature infants during treatment for patent ductus arteriosus, and significant changes may occur between day 3 and day 5 after birth in those infants with a closing ductus. These findings may have implications for the treatment schedule with ibuprofen in patients with patent ductus arteriosus.

Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants

“…As expected, our study demonstrated a lower Cmax than those reported with intravenous ibuprofen administration 30. The interesting finding in our analysis is that the area under the curve (AUC) 0→24 was higher in the oral regimen when compared with the intravenous route, as demonstrated in figure 1.…”

“…Two examined intravenous administration29 30 and only one31 reported ibuprofen pharmacokinetics following oral administration (table 4). …”

Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns

“…The population PK models (see Supplementary File 1) were compared with respect to birth weight, gestational age (GA), and postnatal age (PNA) of the cohort, ibuprofen-dosing regimen, route of administration, and studied ibuprofen enantiomers [12, 22, 23, 30, 31]. …”

“…(R)-ibuprofen is a relatively weak inhibitor of COX-2 [21]. The metabolism of ibuprofen has been shown to mature during early life [12, 22], with CYP2C8 mainly responsible for the metabolism of (S)-ibuprofen, and CYP2C9 for (R)-ibuprofen. The mean half-lives for (S)- and (R)-ibuprofen in preterm infants of about 34 h and 8 h at birth, respectively [23], followed by a very rapid increase of (R)-ibuprofen elimination during the first days of life.…”

Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants

“…In an attempt to support their conclusion, they compare ibuprofen area under the curve (AUC) 0→24 generated by their study with data generated by two studies of intravenous ibuprofen 2 3. This explanation of oral ibuprofen superiority is problematic from several perspectives.…”