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The post-distributive neonatal:maternal plasma salicylate concentration ratio following salicylate administration to the mother before delivery is appreciably higher than unity. The protein binding of salicylate and the albumin concentration in one such plasma pair were considerably higher in the neonatal than in the maternal plasma. Equilibrium dialysis of neonatal plasma or serum from 6 newborn infants against that of their mothers produced a neonatal: maternal salicylate concentration ratio above unity in all cases even if the albumin concentration in the neonatal serum did not exceed that in the maternal serum. However, there was a strong correlation between the neonatal:maternal concentration ratios of salicylate and albumin. These observations demonstrate that conclusions concerning the distribution of a drug across the placenta in relation to its plasma protein binding characteristics must be based on the results of binding studies with plasma or serum from neonates and their mothers, and not from other adult subjects.

Diphenylhydantoin (DPH) elimination was studied in 4 overdosed children who presented with serum concentrations ranging from 44 to 76 mg/l. Serum was assayed for DPH and urine was assayed for both DPH and 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH). The serum and urine data were subjected to simultaneous computer nonlinear regression analysis using a one-compartment pharmacokinetic model, which accounts for much of the known disposition kinetics of DPH. Computed values for the apparent in vivo Michaelis-Menten constants, K-M and V max, were compared with values derived from data in the literature for normal adult subjects. A trend toward relatively lower K-M and higher V max/K-M values was seen in children. Patients with higher V max values had greater urinary excretion rates of HPPH which, at high serum levels of DPH, were relatively constant except for an apparent diurnal rhythm. The time of onset of DPH toxicity in the children was related to the magnitude by which the rate of DPH administration exceeded the V max values.

Extensive animal testing and 30 years of human experience have established the general safety of DEET when applied episodically to skin or bedclothes. Local and systemic toxic and allergic reactions to DEET have been observed in man. Three weeks prior to admission, for the purpose of self-medication, a 30 year old man began daily applications of the insect repellant, DEET followed by a 1-2 hour period in a light-bulb heated box. Sedation and incoherence were noted for short periods following each application session. Aggressiveness and psychotic ideation led to hospital admission where he displayed psychomotor hyperactivity, rapid and pressured speech, tangentiality, flight of ideas, and grandiose delusions. Treatment was begun with haloperidol. Clinical improvement was complete within 6 days, atypical for classic endogenous mania. Drug and metabolites were identified in the urine more than 2 weeks after the last drug application.

The Department of Medicine (Clinical Pharmacology) and the Department of Pediatrics, Emory University School of MedicineRecently, pharmacokinetic interactions between phenobarbital (PB) and diphenylhydantoin (DPH) were described. 3 • 4, 10 Attention has been focused on the hypothesis that PB induces an increase in the rate of DPH metabolism. It was the purpose of the present investigation to assess this in children. Steady-state serum concentrations of these two drugs were followed in a limited number of children. Since the rate of elimination of PB was known only in adults, the rate of decay of serum con-