Abstract
Thaophylline (TH) disposition is known to vary greatly in the neonatal period. Parameters obtained after discontinuation of the drug or after single dose study yield misleading information if the drug has dose-dependent kinetics. Therefore, pharmocokinetic parameters are commonly determined between dosing intervals once steady state has been achieved. The purpose of this study was to evaluate the accuracy of the “in between doses” method in the neonatal population treatad with TH. Nine preterm infants (GA:26-30wk, postnatal age; 7-191d, study weight:0.910-1.803kg] received one pulsed dose of stable isotope labeled thaophylline TH-3 [1,2 15N, 2 13TH), given IV. Blood end urino wera collected for one week. All samples were analysed by selected ion monitoring GC/HS. Phermacokinetic parameters determined from TH decay during one Bh dosing interval were compared to those obtained from tha disappearance curve of TH-3 over one week period. Systemic clearances calculated from AUC indicated thet TH and TH-3 disposition were identical. [paired T test:N.S.] However, TH-3 t1/2 [29 7+14.5H] was significantly longer than TH t1/2 (14.8+6h). The difference cannot be accountad for by a distribution phase since TH t1/2 was calculated 8-16h after the previous dose. Urine data showed an increased excretion of TH following each dose as a result of a diuretic effect. Therefore, the shorter t1/2 obtained from the multiple-dose method reflects a fast decay due to diuresis, while the longer t1/2 obtained from the steble isotope method is the real half-life. We conclude that calculating theophytline half-life between two doses, significantly underestimates the real t1/2 representing potential risk of toxicity.
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Dothey, C., King, K., Kam, S. et al. THE ADVANTAGE OF STABLE ISOTOPE LABELED THEOPHYLLINE FOR STEADY STATE KINETICS IN PREMATURE INFANTS. Pediatr Res 21 (Suppl 4), 233 (1987). https://doi.org/10.1203/00006450-198704010-00404
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DOI: https://doi.org/10.1203/00006450-198704010-00404