Safe use of aminoglycosides requires close monitoring of serum concentrations. Limited information coupled with marked changes in fluid compartments and renal function during the first week of life in premature neonates makes interpretation of peak and trough levels very difficult. This study was designed to measure serum netilmicin levels following a 2.5 mg/kg IV push infusion. Blood samples were taken on the 5th day of therapy 1 hour before and 1, 6, and 11 hours after a dose. Fifteen premature infants weighing 1000-1500 gm at birth and 20 others whose weight ranged from 1501-2750 gm comprised the study population. All premature infants were appropriate for gestational age (AGA) and of them, only two were severely asphyxiated. At the time of the study, 10 neonates were still on respirators. Serum and urine sodium and creatinine, BUN, and urinalysis were obtained in 28 of these infants. No evidence of renal dysfunction was found. All infants received 100 mg/kg IV ampicillin every 12 hours, but none were being treated with diuretics. Serum netilmicin levels were measured by an enzymatic immunoassay, peak and trough were calculated by extrapolating the first order decay curve. Peak levels ranged from 3.4 to 14 micrograms/ml (means 6.1 +/- 2.5 micrograms/ml SD) and 90% of them were above 4 micrograms/ml. Half of the small premature infants (1000-1500 gm birthweight) presented trough values above 3 micrograms/ml. Pharmacokinetic analysis of our data predicts that a 2.5 mg/kg loading dose followed by 2 mg/kg given every 12 hours will decrease by one-half the number of small prematures exceeding the considered "safe" trough level (greater than 3 micrograms/ml).

This study was designed to evaluate the serum concentration of tobramycin sulfate following a 2.5-mg/kg intravenous infusion in 43 premature infants on days 1, 3, and 5 of age (therapy). Twenty premature infants weighing 1500 gm or less at birth and 23 others whose birthweights ranged from 1501 to 2500 gm made up the study population. Serum tobramycin levels were measured by an enzymatic immunoassay (EMIT) at one, four to six, and 12 hours after injection. Peak serum levels increased from day 1 (means, 5.2 +/- 2.2 mcg/ml) to day 3 (means, 6.1 +/- 2.6 mg/ml) and then remained unchanged at day 5 (means, 6.1 +/- 2.4 mg/ml). Approximately 40% of the study population presented trough levels above 2 mcg/ml on day 1 and over 70% on days 3 and 5. No evidence of renal toxicity or auditory dysfunction was observed. In light of the high trough levels observed during the first week of life in premature infants, it may be judicious to monitor serum tobramycin concentration and to decrease the dosage or to prolong the dose interval in order to maintain trough concentrations below 2 mcg/ml.

The placental transfer of xanthine compounds such as caffeine and theophylline has only recently been recognized. By measuring serum theophylline concentrations in two mothers and their neonates at delivery, we have attempted to determine the extent and significance of placental theophylline transfer to the fetus. At delivery, the two maternal serum theophylline concentrations were 13 µg/ml and 11 µg/ml, and cord serum contained 12 µg/ ml and 11 µg/ml of theophylline, respectively. In our first case, the neonatal theophylline concentration at delivery was not reported, but a concentration of 13 µg/ml was obtained six hours after delivery. In the second case, the neonatal serum contained 14 µg/ml of theophylline at delivery, 3 µg/ml higher than the cord or maternal serum concentration. It is possible that the fetus behaves as a pharmacokinetically "deep" compartment with slower drug elimination relative to maternal excretion. Serial serum theophylline concentrations in the neonates were determined at 6, 18, 30, and 40 hours after delivery. For the first 18 hours of life, both neonates' serum contained theophylline within or very close to the therapeutic range (10 to 20 µg/ml) in adults and children. Both neonates reported on in this article had minor clinical symptoms that may have been related to the theophylline present in their serum. Neonates of mothers receiving theophylline products should be monitored for the pharmacologic actions of theophylline.

France. Calcium a n t a g o n i s t s a r e a new c l a s s of drugs which may be u s e f u l during t h e n e o n a t a l p e r i o d. Since t h e i r e f f e c t s on r e g i o n a l blood flows (RBF) had n o t been s t u d i e d , we a s s e s s e d t h e e f f e c t s of IV d i l t i a z e m (DTZ) on hemodynamics and RBF measured w i t h r a d i o a c t i v e microspheres i n urethan-a n e s t h e t i z e d p i g l e t s (age = 5.4 + 0.6 d). S i x p i g l e t s received DTZ (0. 5 and

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