Maturational ch&ges in T pharmacokinetics were evaluated in 45 infants; postconceptional age (PCA) 30.9-95.7 wks. After achievement of steady-state on T maintenance therapy, multiple serum and urine samples were obtained over dosing interval and assayed by HPLC f o r T and ~netabolites: caffeine (C), 1-methyl uric acid (IMU), 3-methylxanthine (3MX), 1,3-dimethyluric acid (1,3MU). Mean(S0) T clearance (Cl) increased significantly (~( 0 . 0 5 ; ANOVA) for PCA groups a t 30-40, 40-50 and >50 wks from 2 1 . 9 ( 6 . 3 ) t o 2 6 . 6 ( 7 . 7 ) and 57.7(17.6) m l l h r l k g , respectively. Concomitant decrease (p<0.05) in serum CIT r a t i o was observed for same PCA groups; 0.43(0.15), 0.22(0.07) and 0.06(0.1), respectively. Significant serum C concentrations (CIT>O.10) were found in some infants up to 55 weeks PCA. Stepwise mu1 t i p l e regression analysis showed urinary excretion of 3MX to be the primary parameter explaining the change in both T C1 (r.0.81, pC0.01) and serum CIT r a t i o ( r = 0 . 6 6 , p<0.01). Urinary excretion of 3YX (demethylated) for the 3 PCA groups was 1.4, 4.2 and 13.1% c q a r e d to 23%, 41% and 44% for 1,3MU (oxidative). Disappearance of serum C and maturation of T metabolism i s dependent on development of demethylation pathway which does not occur until approximately 55 wks PCA. Prior to that age, serum C concentration should be monitored i n patients receiving T.Children's and S t e ust tine Hosp, Montreal, Canada. Low doses of Id may d e c r e a s e t h e incidence of i n t r a v e n t r i c u l a r hemorrhage i n prem NB, but i t s e f f e c t on immature c e r e b r a l v a s c u l a t u r e and more s p e c i f i c a l l y post endotracheal suctionfng i s unknown. Using Doppler technique, 13 prem N B t r e a t e d w i t h Id f o r t h e treatment of p a t e n t d u c t u s a r t e r i o s u s were studied. CBFV of a n t e r i o r c e r e b r a l a r t e r i e s calculated from the area under t h e v e l o c i t y c u r v e (AUTC/min), heart r a t e (HR), and mean a r t e r i a l pressure (MABPI were recorded before and 15, 30, 45, 60, and 120 min a f t e r t h e 1 s t IV i n j e c t i o n of Id 0.2 mg/kg (group l , BW: 1269 2 353 ern, CA: 29 2 2 wks), and t h e 3rd i n j e c t i o n (group 2, BW: 1490 2 459 gm, G A : 30 + 3 wks). C a p i l l a r y blood g a s e s were obtained before and 60 min a f t e r drug injection. MABP, HR, blood gases and p u l s a t i l i t y index were s t a b l e throughout t h e study i n both groups. The 1 s t dose of Td decreased CBFV a t 15 min b y 22%. and was s u s t a i n e d t i l l 120 min (-285, pi0.005). CBFV v a l u e s before 1 s t and 3rd i n j e c t i o n were comparable. CBFV did not change a f t e r t h e 3rd dose. I n 5 mechanically v e n t i l a t e d i n f a n t s , AIIvC was a l s o measured pre and post endotracheal suctioning, before and 60 min a f t e r each i n j e c t i o n . I n group 1 , t h e percent i n c r e a s e i n CBFV secondary t o suctioning was 21.38 2 27.26 % before Id and 2.77 2 28.45% 60 min a f t e r J d (~< ...