Chloral hydrate disposition following single-dose administration to critically ill neonates and children.
Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been studied in healthy adults, no comprehensive studies have been done in neonates and young infants. Major physiological differences between these groups could greatly affect drug disposition. In this study the patient population (22 patients) was divided into three groups according to postconceptual age: group 1 = preterm infants (31-37 weeks), group 2 = fullterm infants (38-42 weeks) and group 3 = toddler-child patients (57-708 weeks). After receiving one 50 mg/kg oral dose of CH, the parent drug and its metabolites were determined by gas chromatography utilizing an electron capture detector. CH, contrary to what has been reported in the adult, was detectable for several hours after oral administration to patients in all three groups. A highly significant negative correlation was observed amongst the three groups for the half-life (t1/2) and area-under-the-curve for 0 to infinity values for trichloroethanol (TCE), the active metabolite responsible for the sedation effect. The t1/2 value for TCE in group 3 (9.67 h) was similar to that reported for the adult population, but in the less mature subjects it was approximately three (group 2: 27.8 h) to four times (group 1: 39.8 h) greater. Trichloroacetic acid had a remarkably long residence time in the study population after a single dose of CH. The concentration of this metabolite failed to decline even 6 days after dose. These issues should be carefully considered when CH administration is contemplated for clinical use in neonates, infants and children.
Perinatal Research Laboratory, Neonatal Services, College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
D J
DJ
Mayers
K W
KW
Hindmarsh
K
K
Sankaran
D K
DK
Gorecki
G F
GF
Kasian
D000284:Administration, Oral; D000293:Adolescent; D000375:Aging / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002697:Chloral Hydrate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature
D002697:Chloral Hydrate