We examined the pharmacokinetic properties of naloxone in a group of premature infants infused with an intravenous bolus of the drug. Ten infants with a mean birth weight of 1,328 ± 402 g and a gestational age of 29.4 ± 2.8 weeks were studied at an age of 4.5 ± 3.2 days of life. Following administration of 0.4 mg/kg of naloxone, we obtained blood samples at specific time intervals, and stored the serum for later analysis by a radioimmunoassay method. Calculations from the serum concentration versus time relationship resulted in an elimination rate constant of 0.75 ± 0.39/h, a half-life of 70.5 ± 35.2 min, a systemic clearance of 39.13 ± 14.53 ml/min/kg, and an apparent volume of distribution of 3.52 ± 1.20 liters/kg.

No abstract

The skin is a common target organ of adverse drug reactions.These reactions may be mediated by toxic drug metabolites. 2 vitro approximations of this process allow a non-invasive assessment of pathogenetic mechanisms. keratinocytes (K) contain cytochrome P450 oxidases and detoxification enzymes. Acetaminophen (APAP) toxicity results from P45O-generated metabolites which deplete cellular glutathione (GSH) and bind to macromolecules. Human K from a squamous cell carcinoma line (A431) were incubated with APAP (0, 1.0, 6.0, and 20 nM).Toxicity, expressed as percent of dead cells by trypan blue exclusion, revealed 6.4 * 1.0%, 9.5 2.4%, 39.1 * 1.2%, and 45.3 f 6.2% respectively. GSH was depleted to 56.8% of baseline at 20 nM APAP. After incubation with 20 nM APAP for 5 hr, cells were grown overnight in cysteinefree medium, 0.1 mM L-cysteine, or 0.25 mM N-acetyl cysteine, 373.4+197 The mean plasma t 112 of (I) in these infants (71.3+39.1 h;s) was significantly prolonged when compared with previously reported values. Furthermore the mean plasma t 112 of (I) was significantly longer in the .250pg 7 days following (I).These data strongly suggest that previously recommended dosages of (I) for very low birth weight infants in the first 48 hrs. may result in very elevated and prolonged levels. PHARMACOKINETICS OF NALOXONE IN PREMATURE INFANTS.392 I n a L, S t i l e , Maria F o r t , Francoise Marotta, Robert k u r z b u r g e r , I. Mark t i i a t t , Thomas Hegyi, UMDNJRutgers Medical School and School o f Pha,rmacy, S t . P e t e r ' s Medical Center. Deot. o f P e d i a t r i c s . New Brunswick. N. J . Raoid d i s io o e e r a n c e o f n a l o x o n i was observed i n a arouo o f very l o w b i r t h w e i g h t i n f a n t s examined f o r naloxone k i n e i i c s . F i v e i n f a n t s (BW 1 .20+0.25kg, GA 292lwk) r e c e i v e d 0.04 mg/per kg o f naloxone i n t r a v e n o u s l y , f o u r w i t h i n t h e f i r s t week o f l i f e and one on day 26. S e r i a l serum samples were o b t a i n e d a t spec i f i c time i n t e r v a l s and frozen f o r subsequent a n a l y s i s . Serum naloxone c o n c e n t r a t i o n s were measured by t h e radioimmunoassay method o f Berkowi t z (1 975).S e r i a l naloxone c o n c e n t r a t i o n a t 5 min. was 51.5+13.4pmole/ ml, a t 15 min. 36.7+4.0pmole/ml, a t 30 min. 28.9+5.lpmole/ml, a t 60 min. 20.4+5.9pmole/ml, a t 120 m i n . 7.3+2.4pmole/ml, and 240 min. 1 .5+0.4pmole/ml.No naloxone was d e t e c t e d a t t h e n e x t sample t i m e ( 1 2 h r s ) . The e l i m i n a t i o n r a t e c o n s t a n t (Ke) c a l c ul a t e d from t h e decay p o r t i o n o f t h e e l i m i n a t i o n curve was 0.8231 0.130/hr.The c a l c u l a t e d h a l f l i f e ( t k ) was 51.829.2min. No c o r r e l a t i o n s were found between Ke and t 4 and i n i t i a l serum l e v e l , b i r t h w e i g h t , g e s t a t i o n a l age, and p...