Pregnant Long-Evans rats were fed stock diets containing 50 or 100 mg/kg of added nicotine during days 10-20 or 0-20 of pregnancy. Control rats were given stock diet during days 0-20. The mean nicotine intake ranged up to 6.03 mg/kg/day. In fetuses bled on day 20 there were no differences in levels of fetal plasma triglycerides, phospholipids, and cholesterol between the experimental and control groups. In another experiment single doses of 1 mglkg

This i n h i b i t i o n has been demons t r a t e d i n s e v e r a l i n -v i t r o systems, but a t c o n c e n t r a t i o n s( > 18pg/ml) which might n o t b e achieved i n v i v o w i t h t h e dosage conanonly employed i n t r e a t m e n t of asthma. This s t u d y i nv e s t i g a t e d t h e p o s s i b i l i t y t h a t t h eo p h y l l i n e , a s commonly used f o r asthma therapy, might a l s o i n h i b i t mediator r e l e a s e . 7 a t o p i c s u b j e c t s (6 a s t h m a t i c c h i l d r e n and an a d u l t w i t h hayfever) had leukocyte h i s t a m i n e r e l e a s e determined w i t h ant i g e n s t o which they were s e n s i t i v e . Release was measured a t 8 a.m. and 1 2 noon on 2 c o n t r o l days and on a drug day, on which t h e o p h y l l i n e 6mg/kg was given o r a l l y a t 8 a.m. Plasma t h e o p h y l l i n e l e v e l s were determined on each specimen of blood drawn f o r h i s t a m i n e r e l e a s e . 3 s u b j e c t s had up t o 38% i n h i b it i o n o f histamine r e l e a s e by t h e o p h y l l i n e ; t h e o t h e r 4 pat i e n t s showed no e f f e c t . 2 of t h e 3 s u b j e c t s who showed i n h ib i t i o n had plasma t h e o p h y l l i n e l e v e l s i n excess of 10pg/ml; a l l of t h e unresponsive s u b j e c t s had l e v e l s l e s s than 10,ug/ml. The plasma l e v e l achieved by a g i v e n dose of t h e o p h y l l i n e i s extremely v a r i a b l e among p a t i e n t s , but i n some p a t i e n t s leve l s a r e achieved which w i l l i n h i b i t mediator r e l e a s e . This s u g g e s t s t h a t i n some a s t h m a t i c c h i l d r e n t h e o p h y l l i n e may have b e n e f i c i a l e f f e c t s o t h e r t h a n bronchodilatation.RELATIONSHIP BETWEEN DOSE AND APPARENT VOLUME OF DISTRIBUTION OF SALICYLATE I N CHILDREN. Gerhard Levy and Sumner J . Yaffe, Departments of Pharmaceutics and P e d i a t r i c s , S t a t e U n i v e r s i t y of New York a t Buffalo.The purpose of t h i s i n v e s t i g a t i o n was t o determine the r e l a t i o n s h i p between dose and t h e d i s t r i b u t i o n of s a l i c y l a t e i n t h e body. The apparent volume of d i s t r i b u t i o n was determined from t h e c o n c e n t r a t i o n of s a l i c y l a t e i n plasma o r serum a t v a r i o u s times a f t e r s a l i c y l a t e i n g e s t i o n and from t h e amount of d r u g remaining i n t h e body a t t h e s e times a s a s s e s s e d from u r i n a r y e x c r e t i o n d a t a . These s t u d i e s were c a r r i e d o u t on eleven c h i l d r e n , 4 months t o 16 y e a r s o l d , who had ingested from about 36 t o over 340 mg. s a l i c y l i c acid (mainly a s a s p i r i n ) per kg. of body weight. The apparent volume of d i s t r i b u t i o n of s a l i c y l a t e ranged from 162 t o 345 ml./kg. and increased w i t h i n c r e a s i n g dose. This means t h a t plasma s a l i c y l a t e c o n c e n t r a t i o n s i n c h i l d r e n who have ingested l a r g e doses of t h e drug a r e p r o p o r...