Variability of serum indomethacin concentrations after oral and intravenous administration to preterm infants

Abstract

Fifteen preterm infants with patent ductus arteriosus and respiratory distress syndrome were given indomethacin (0.2 mg/kg) at 12 h intervals up to three times, either orally or intravenously, in an uncontrolled, non-randomized study. Serum indomethacin concentrations were determined in blood samples taken 12 h after dosing. There was considerable variability in the serum indomethacin concentrations, especially after oral administration, although the mean concentrations after each of the three doses were similar after both oral and intravenous administration. The frequency of closures and transient closures of the ductus arteriosus was also similar for both routes of administration. There was, however, no relation between concentration and effect in individual patients. The sustained exposure to indomethacin which appears to be necessary for ductal closure can sometimes be attained by oral administration.

Determination of indomethacin in plasma by micellar electrokinetic chromatography with UV detection for premature infants with patent ducts arteriosus

“…The simple CZE method had been reported for determination of indomethacin in plasma and its detection limit is 3 g/mL [26]. The therapeutic level of indomethacin, however, is 0.5-2.5 g/mL.…”

“…An alternative would be orally administered indomethacin (0.2 mg/kg) at 12 h intervals up to three times. In a previous report, the frequency of closures and transient closures of the ductus arteriosus was similar for both routes of administrations [26]. Three premature infants with PDA were administered indomethacin by enteral route at an initial dose of 0.2 mg/kg at the Department of Pediatrics intensive care ward.…”

A rapid and sensitive microscale HPLC method for the determination of indomethacin in plasma of premature neonates with patent ductus arteriousus

“…The assay imprecision and inaccuracy are presented in Table 1. The lower limit of quantification (LOQ) was set a priori at 35 g/L, the concentration at which the inaccuracy was less than 10% and the intra-day imprecision was <15% and which was sufficiently low to measure IND concentrations following administration to neonates from a previous study [4], and from our own patients (Fig. 3).…”

“…Of these, indomethacin (IND) has long been the drug of choice for treating PDA. Indomethacin is extensively bound to plasma proteins [2], and has wide intersubject variability in the plasma concentrations, half-life and therapeutic response in premature neonates [3][4][5]. Our interests lay in correlating dose and IND plasma concentrations with outcome in PDA and in estimating its population pharmacokinetics and absolute bioavailability in premature neonates.…”

Furosemide in indomethacin-treated infants - systematic review and meta-analysis

“…Is is therefore difficult to assess the amount of drug absorption, which has been reported by others to vary between 10% and 90% in premature infants [29][30][31]. For the study of Vargas-Origel et al [28], Fig.…”