The disposition of alfentanil in neonates with respiratory distress.
The disposition of continuous infusion alfentanil was evaluated in 13 mechanically ventilated neonates (gestational age 37.6 +/- 2.4 wks) with hyaline membrane disease (n = 7) or persistent pulmonary hypertension of the newborn (n = 6). Alfentanil was administered as a loading dose 8 micrograms/kg, followed by a variable-rate continuous infusion (maximum 10 micrograms/kg/hr; minimum 2.5 micrograms/kg/hr) for 27 hours. Serial plasma samples were obtained for pharmacokinetic analysis. Noncompartmental pharmacokinetic analysis of the data revealed the following estimates (mean +/- SD): total-body clearance 3.24 +/- 2.23 ml/kg/minute, volume of distribution 0.54 +/- 0.21 L/kg, and elimination half-life 4.14 +/- 2.58 hours. A significant effect of alfentanil plasma concentration on total-body clearance was found (r = -0.75; p = 0.02), suggesting nonlinear pharmacokinetics. No correlation was seen between total-body clearance and alfentanil dose (r = -0.37; p = 0.32). The results suggest that a larger dose-proportionality study is required to determine the linearity or nonlinearity of alfentanil pharmacokinetics in neonates.
Wiest
D B
DB
Department of Clinical Pharmacy, Medical University of South Carolina, Charleston 29425.
Ohning
B L
BL
Garner
S S
SS
D015760:Alfentanil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D006819:Hyaline Membrane Disease / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010547:Persistent Fetal Circulation Syndrome / Q000378:metabolism*; D012121:Respiration, Artificial
D015760:Alfentanil