Abstract 1068 Poster Session I, Saturday, 5/1 (poster 74)

There are few data concerning the pharmacokinetics of the life-preserving hormone cortisol (F, hydrocortisone) in extremely premature neonates. This study aimed to remedy this knowledge deficit. As neonates are known to have endogenous pulses of cortisol (F) secretion we chose to study infants receiving dexamethasone (DEX) for chronic lung disease (CLD) in whom such endogenous secretion should be suppressed.

After parental consent, we studied 6 intubated infants (5 female, 1 male; 5 AGA, 1 SGA) of mean (range) BW 653 g (530-980) and gestation 24.8 wks (24-26) at a mean (range) postnatal age of 30 days (23-40). While on DEX for CLD, all 6 infants received a single intravenous dose of hydrocortisone sodium succinate (HCSS), 0.8 mg/kg. Blood samples for plasma F estimation, by RIA, were taken via an indwelling arterial line at -4, -3, -2, -1 and 0 hours before the HCSS injection and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 8, 10, 12, 18, 24 and 30 hours post injection. The sampling times for plasma F were chosen as the only two previous estimates of elimination half-life (T1/2) in extremely premature neonates ranged from 45 mins to 12 hours. A single corticosteroid-binding globulin (CBG) level was estimated by RIA on each infant.

All pharmacokinetic parameters were calculated model independently. Background plasma F levels were obtained by meaning the plasma F concns before the HCSS dose and more than 8 hours post dose. Results are given as mean ± SD (range): (Table) All six neonates showed evidence of non-linear or dose (concentration) - dependent pharmacokinetics.

Table 1 No caption
Full size table

We conclude that extremely premature infants receiving DEX for CLD, studied in the postnatal range of 23-40 days, have short terminal elimination half-lives for hydrocortisone, with a mean value of 38 mins. We hypothesize that zero order pharmacokinetics are operating at higher plasma F concns (eg. post HCSS administration) and first order pharmacokinetics operate at lower plasma F concns.