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The purpose of this study was to determine the dose requirements and dose interval of a sustained-release theophylline sprinkle preparation (Somophyllin-12) necessary to maintain therapeutic serum theophylline concentrations in children with asthma. Eighteen patients aged 3-7 years (subgroup 1) and 21 patients aged 8-12 years (subgroup 2), who had been on continuous theophylline therapy with Somophyllin-12, completed the study. Prior to entry into the study, each patient's dosage of Somophyllin-12 was titrated to achieve predose and peak (4-hour postdose) theophylline levels in the therapeutic range (8-20 mg/L). The patients subsequently had predose and peak serum theophylline levels determined at baseline (week 0) and at weeks 2 and 4 of the study. The majority of children maintained theophylline levels in the therapeutic range throughout the 4-week trial, and t-tests showed no significant change from baseline in mean values of peak, trough, or peak-trough theophylline differences in either patient subgroup at weeks 2 and 4. Nevertheless, some individual patients had considerable variation from baseline in peak and trough theophylline levels at follow-up visits. Dosage requirements standardized for weight were significantly higher in patients in subgroup 1 than in subgroup 2 (21.3 +/- 4.5 mg/kg per day versus 17.5 +/- 4.7 mg/kg per day; p less than 0.05). The majority of the patients required 12-hourly administration of Somophyllin-12, but seven of 39 patients required 8-hour dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

14 C-Tetrahydrocannabinol (THC) was injected i.v. into a total of 92 adult Wistar rats. At 14 times ranging from 2 min to 48 hr afterwards, groups of animals were examined for total 14 C activity and thin-layer chromatographic (TLC) pattern of 14 C distribution in blood, brain, heart, kidney, liver, lung, muscle, spleen and perirenal fat. The time course of rise and fall of radioactivity in the various organs and tissues closely resembled that of thiopental and other strongly lipophilic substances. Relatively high levels persisted in fat 48 hr, but levels in brain were quite low. TLC analysis showed the early appearance of 7-hydroxy-THC in all tissues, followed by increasing amounts of more polar compounds and disappearance of THC, except in fat. Levels were much lower after i.p. injection, and whole body autoradiography showed most of the activity remaining in the peritoneal cavity.

(Na+ + K+)-dependent ATPase [(Na + K)-ATPase] and K+-dependent p-nitrophenyl phosphatase [pNPPase] activities in rat brain heavy microsomal fractions were studied in the presence of 120 mM Na+ and varied concentrations of K+, Rb+, Cs+, Li+ or NH4+. Scatchard and Hill plots indicated non-hyperbolicity (cooperativity) with all except Li+, which supported a considerably lower activity than any of the other ions tested. Addition of 0.22 M ethanol to the incubation mixtures produced a formally competitive inhibition of ATPase activity with K+, Rb+ and Cs+, a non-competitive inhibition with Li+, and a mixed inhibition with NH4+. The changes in pNPPase activity generally followed a similar but less clear-cut pattern. The values of the Hill constants were not changed for either enzyme activity. The findings are interpreted as evidence that ethanol inhibits ATPase activity by inducing conformational changes which alter the consequences of ion binding to the various receptor sites.

Rats were rendered tolerant to either morphine or alcohol, by 21 day drug treatment. Morphine treatment induced a decrease in the degree of incorporation of (3H)-phenylalanine into pro-opiomelanocortin (POMC), β-lipotropin (β-LPH) and β-endorphin (β-EP) associated with a decrease in the content of β-endorphin like immunoreactivity (β-EPLI) in the neurointermediate lobe (NIL) extract and in the incubation medium. Alcohol induced an increase in the degree of incorporation of (3H)-phenylalanine into POMC, β-LPH and β-EP and an increase in the β-EPLI content in the incubation medium but not in the NIL extract. These results indicate an effect of chronic morphine and alcohol treatment on the biosynthesis and release of β-EP by the rat NIL.

Rats were rendered tolerant to either morphine or alcohol, by 21- day drug treatment. The neurointermediate lobes (NIL) were removed and incubated with [3H]-phenylalanine for 3 hrs. The biosynthesized pro-opiomelanocortin (POMC), β-lipotropin (β-LPH) and β-endorphin- like peptides (β-EPLPs) were purified from the total protein extract of the NIL by immunoprecipitation with an antiserum to β-endorphin (β-EP), and analyzed by sodium dodecyl sulfate polyacrylamide disc gel elecrophoresis. The β-EPLPs were further characterized by extraction from the gel and microsequencing. The homology of rat POMC to authentic bovine POMC was established by extraction from the gel and peptide mapping of its tryptic digestion products. Furthermore, the β-endorphin like immunoreactivity (β-EPLI) was estimated in the incubation medium and in the NIL extract. The morphine treatment induced a decrease in the degree of incorporation of [3H]- phenylalanine into POMC, β-LPH and β-EPLPs, associated with a decrease in the content of β-EPLI in the NIL extract and in the incubation medium. Alcohol induced an increase in the degree of incorporation of [3H]-phenylalanine into POMC, β-LPH and β-EPLPs, and an increase in the β-EPLI content in the incubation medium, but no change in the β-EPLI in the NIL extract. These results indicate an effect of chronic morphine and alcohol treatment on the biosynthesis and release of β-EPLPs by the NIL.