A serum concentration profile study on midazolam in children was done. Fifty six children aged 3-10 years took part. The routes investigated were intravenous, intramuscular, rectal and oral at 0.15 mg.kg-1, and the oral at 0.45 mg.kg-1 and 1 mg.kg-1. Serum concentration levels for 5 h were studied using gas liquid chromatography. The volume of distribution, Vss, was 1.29 l.kg-1, the elimination half-life 1.17 h and the serum clearance 9.11 ml.kg-1.min-1. Peak serum concentrations for the intramuscular, rectal and oral routes were at 15 min, 30 min and 53 min respectively. Bioavailability was 87%, 18%, 27% respectively at a dose of 0.15 mg.kg-1. The oral route bioavailability halved to 15% at the two higher doses. Bioequivalence was present between the 0.15 mg.kg-1 intramuscular dose and the 0.45 mg.kg-1 oral dose from 45 to 120 min.

No abstract

A technique for the organ culture of postnatal and adult rat liver has been developed. Liver slices, 0.3 mm thick, were maintained in Conway units at the interphase between medium and a 95% O2:5% CO2 atmosphere. Postnatal liver in culture for up to 72 h had healthy hepatocytes throughout the explants; if adult liver was used the upper 0.2 mm was healthy after 24 h. These slices incorporated tritiated orotate and leucine into trichloroacetic acid-precipitable material. Incorporation of orotate was shown to be spread over the entire slice of neonatal liver. Culturing did not alter the potassium ion content of postnatal liver. Tyrosine aminotransferase activity in liver slices from postnatal, adult, and adrenalectomized adult rats was stimulated by glucocorticoids and dibutyryl cyclic AMP. Cycloheximide and actinomycin D prevented this response. Further, cortisol exerted a permissive effect on the stimulation of tyrosine aminotransferase activity by dibutyryl cyclic AMP in slices from adrenalectomized rats. Induction of urea cycle enzymes by cortisol was demonstrated in cultures of liver from adrenalectomized adult animals.

When 6-week-old rats fed normal diet (22% protein) were transferred to 10 and 7 5 % protein diet, the levels of urea cycle enzymes showed decreases and increases respectively. The activities expressed as units per gram wet weight of liver had not stabilized after 7 days on the new diet; the corresponding specific activities were closer to leveling off. Four daily injections of cortisol raised CPS, ASS, and arginase. The percentage increases were greater on a 10 than on a 75% protein diet. Adrenalectomy of rats fed 10% protein decreased all urea cycle enzymes; on 7 5 % protein, only arginase decreased. All enzymes could be raised to control levels within 24 h by three injections of cortisol. Thyroxine produced only slight increases in urea cycle enzymes. On a 10% protein diet, all five enzymes were raised by thyroidectomy, and further raised by injection of thyroxine.