Sodium Phenobarbitone Research Articles

Studies on the properties of highly purified cytochrome P-448 and its dependent activity benzo[a]pyrene hydroxylase, from Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae, produces a cytochrome P-450 enzyme with a Soret peak in the reduced-CO difference spectrum at 448 nm. The enzyme purified to homogeneity (88-97% pure on a specific content basis) has a molecular wt. of 55 500 as determined by SDS-PAGE. Amino acid analysis of yeast cytochrome P-448 revealed 407 amino acid residues per molecule with a 43% complement of hydrophobic residues. Although the number of residues is smaller than cytochrome P-448 enzymes from mammalian sources, the percentage of hydrophobic residues is almost identical. Estimation of the haem content of yeast cytochrome P-448 showed that one haem group was present per molecule. Phospholipid was present at very low levels. The molecular wt. of the polypeptide chain plus an estimated 5-6 units of hexose and of hexosamine is in good agreement with the molecular wt. value obtained from SDS-PAGE. A reconstituted system of purified cytochrome P-448, purified NADPH-cytochrome P-450 (c) reductase and phospholipid showed aryl hydrocarbon hydroxylase activity towards benzo[a]pyrene. Both protein components, NADPH and dilauroyl phosphatidylcholine (or emulgen 911) were necessary for full activity. The NADPH requirement could be replaced by cumene hydroperoxide or H2O2 generated in situ from a glucose oxidase system; in each case Vmax is increased, but the apparent affinity for benzo[a]pyrene, as measured by an increased Km, is lowered. The spin state of purified yeast cytochrome P-448 was 94% low spin (22 degrees C) as determined from the temperature-dependent spin-state equilibrium. The addition of benzo[a]pyrene to this enzyme resulted in a change to higher spin state (18% high spin at 22 degrees C). Equilibrium gel filtration analysis of the number of benzo[a]pyrene binding sites per mole of enzyme monomer showed a value of 1 for purified yeast cytochrome P-448 and 6 for this enzyme in microsomal form. The corresponding values for purified and microsomal cytochrome P-450 from phenobarbital-pretreated rats are 1 and 6, respectively. However, purified cytochrome P-448 from beta-naphthoflavone-induced rats gave a value of 6 benzo[a]pyrene binding sites. Type I binding spectra with purified yeast cytochrome P-448 were observed with benzo[a]pyrene, lanosterol, ethylmorphine, dimethylnitrosamine, sodium phenobarbitone and perhydrofluorene. Type II spectral changes were observed with imidazole, aniline and benzphetamine. Cytochrome P-448 from Saccharomyces cerevisiae is identified as a distinct enzyme of the P-450 family. This enzyme however has many properties in common with cytochrome P-448 from mammalian sources.(ABSTRACT TRUNCATED AT 400 WORDS)

The influence of barbiturate drugs on tetraethylammonium induced contractures of the chick biventer cervicis muscle in vitro

1. 1. Methohexitone sodium (METHO) 8.8 × 10 −5 M markedly potentiates tetraethylammonium (TEA)-induced contractures of the chick biventer cervicis muscle in vitro, (Elliott, 1979). 2. 2. A group of barbiturates were compared with METHO for their ability to potentiate TEA induced contractures. 3. 3. The concentrations of TEA which produced a 50% maximum contracture (EC 50) in the presence of METHO (8.8 × 10 −5 M and in the optimum potentiating concentrations of the other barbiturates were determined. 4. 4. The EC 50 ratios (= EC 50 METHO/EC 50 test drug) were: barbitone sodium 0.25, phenobarbitone sodium, 0.20, pentobarbitone sodium 0.90, thiopentone sodium, 2.43. 5. 5. The concentrations of the barbiturates used were: barbitone 3.1 × 10 −2 M, phenobarbitone 3.15 × 10 −3 M, pentobarbitone 6.04 × 10 −4 M, thiopentone 1.89 × 10 −4 M. 6. 6. The EC 50 ratios were adjusted by dividing by the ratio [test barbiturate]/[METHO]. 7. 7. The adjusted ratios gave the following potencies (METHO = 1), barbitone 7.13 × 10 −4, n = 6, phenobarbitone 5.58 × 10 −3, n = 8, pentobarbitone 1.33 × 10 −1, n = 6, thiopentone 1.13, n = 6. 8. 8. The potencies correlate well with the partition coefficients of the barbiturates between cell membranes and buffer ( P m/b). 9. 9. The regression y = 1.49 x - 3.12, where y = log (adjusted ratio) and x = log ( P m/ b) fits data with a correlation coefficient of 0.99.

Control of follicle-stimulating hormone secretion by steroid-free bovine follicular fluid in the ovariectomized rat.

The effects of steroid-free bovine follicular fluid (bFF) and sodium phenobarbitone on spontaneous LH releasing hormone (LHRH)-induced secretion of FSH and LH were studied in ovariectomized rats. Luteinizing hormone releasing hormone was administered by infusion to rats anaesthetized with phenobarbitone. Bovine follicular fluid reduced FSH release and synthesis. Luteinizing hormone release remained unaffected after bFF treatment. Phenobarbitone reduced both FSH and LH release. The observed suppressive effects of bFF and phenobarbitone on FSH secretion were additive, suggesting that the basal release of FSH has an LHRH-dependent and an LHRH-independent component. Furthermore, bFF did not affect pituitary responsiveness of LH secretion to LHRH and reduced the responsiveness of FSH secretion only when administered some time before the LHRH challenge. The present observations support the view that in the ovariectomized rat the pituitary gland is the only site of action of inhibin-like activity as present in bFF.

Effects of some antiepileptic drugs on the repetitive activity of the node of Ranvier.

1 Effects of some antiepileptic drugs on the repetitive activity of the node of Ranvier have been tested on frog myelinated nerve fibres. 2 Nerve fibres were stimulated by supraliminal direct current pulses of long duration. Motor fibres responded with a single action potential; sensory fibres responded with repetitive firing at a frequency of about 300/s. Chlordiazepoxide hydrochloride (0.1 mM), phenobarbitone sodium (0.25 mM) or diphenylhydantoin sodium (0.5 mM) suppressed the repetitive activity. 3 Sensory and motor nerve fibres stimulated by a 10 kHz alternating current of strength twice the threshold responded with repetitive firing at a frequency of 400-500/s. Superfusion of the node with chlordiazepoxide hydrochloride (0.2 mM), phenobarbitone sodium (0.5 mM) or diphenylhydantoin sodium (1.7 mM) reduced the frequency of firing by 50% either in sensory or in motor fibres activated by a.c. stimulation; at the same concentrations, the drugs altered amplitude of the action potential and threshold for electric excitability by less than 10%. 4 Unlike local anaesthetics, chlordiazepoxide, phenobarbitone and diphenylhydantoin are more selective in inhibiting repetitive firing than in reducing the amplitude of the action potential or increasing the threshold for electric excitability. 5 Trimethadione (up to 5 mM) was ineffective on repetitive firing elicited either with direct or with alternating current.

Prostaglandins, angiotensin and blood pressure in pregnant rabbits.

A total of 24 rabbits between days 26–29 gestation (term 31 days) were studied acutely. Five does had been pretreated with oral doses (40 mg p.d.) of a prostaglandin synthetase inhibitor (Flurbiprofen) since day 7 of gestation. Rabbits were anaesthetised with sodium phenobarbitone, 30 mg kg−1, and breathed spontaneously. The pressor response to stepwise increments of infused angiotensin II (AII) over the range 16–64 ng kg−1 min−1 was determined in all animals. The 19 does which had not received Flurbiprofen were then subdivided into 4 groups, receiving infusions either of normal saline, 0.1 ml min−1 (n=6) or prostaglandin E1 (PGE1) at 10 ng kg−1 min (n=4), 20 ng kg−1 min (n=5) or 50 ng kg−1 min−1 (n=4). The infusions of AII were then repeated during the additional infusion.The administration of Flurbiprofen was associated with increased basal systolic and diastolic blood pressures. The doses of AII given evoked clear and consistent increases in both systolic and diastolic blood pressure. The previous admi...

Effects of naloxone and naltrexone on the increased water intake and drinking duration in phenobarbitone-treated rats.

In two experiments, phenobarbitone sodium (30 mg/kg) reliably enhanced water consumption and extended the duration of drinking in 24h water-deprived male rats. The opiate receptor antagonists naloxone (0.1-10 mg/kg) and naltrexone (0.1-10 mg/kg) both decreased water intake and reduced the duration of drinking. When the barbiturate was given in conjunction with either naloxone or naltrexone, phenobarbitone and the opiate antagonist exerted opposite effects on the two measures of drinking. While it was true that both opiate antagonists reduced water intake and drinking duration in barbiturate-treated animals, the barbiturate-induced enhancement of drinking was in no way modified by concurrent opiate antagonist treatment. Hence, the effects of phenobarbitone and of the two opiate antagonists upon the drinking measures appeared to be quite independent. There was no evidence, therefore, that the effects of phenobarbitone upon drinking were related to endogenous opioid mechanisms. The possible contrast between benzodiazepine- and barbiturate-induced hyperdipsia is briefly considered in the light of these results.

Studies on the effects of orally administered dicyclohexyl phthalate in the rat.

The oral administration of 500-2500 mg/kg/day dicyclohexyl phthalate (DCHP) to young male Sprague-Dawley rats for 7 days resulted in liver enlargement and induction of some parameters of hepatic xenobiotic metabolism. Additional studies indicated that the hepatic enzyme induction resembled that of sodium phenobarbitone rather than that of polycyclic hydrocarbons. Morphological examination of the livers of DCHP treated rats revealed centrilobular cell hypertrophy and ultrastructural examination demonstrated marked proliferation of the smooth endoplasmic reticulum. Mitochondrial structure and numbers of peroxisomes (microbodies) were not affected. DCHP treatment did not affect kidney and testes weights but some histological evidence of testicular damage was obtained with 2500 mg/kg/day of DCHP. The metabolites of DCHP, namely monocyclohexyl phthalate (MCHP) and cyclohexanol, also induced certain parameters of hepatic xenobiotic metabolism. MCHP, but not cyclohexanol also produced marked testicular atrophy. It is concluded that DCHP is a weak drug-type inducer of hepatic xenobiotic metabolism in the rat and the hepatic effects of this phthalate diester are different from those of di-(2-ethylhexyl) phthalate.

The effects of dietary lipid and phenobarbitone on the production and utilization of NADPH in the liver. A combined biochemical and quantitative cytochemical study.

The validity of the concept that cellular NADPH utilization in the cytoplasm can, by quantitative cytochemical procedures, be classified into two pathways (Pathway I, in which NADPH is oxidized via the microsomal electron-transport system, and Pathway II, in which NADPH supplies reducing equivalents for biosynthetic processes) was tested. The amount of NADPH, generated by glucose 6-phosphate dehydrogenase, entering Pathways I and II in the centrilobular and periportal regions was measured by quantitative cytochemistry, and the values obtained were compared with biochemical measurements of mixed-function oxidase and fatty acid synthetase activity after the administration of sodium phenobarbitone or by altering the quantity and nature of the dietary lipid. Phenobarbitone stimulates hepatic mixed-function oxidation measured biochemically and Pathway I, but not Pathway II. Variation in the type and quantity of dietary lipid can also regulate the activity in mixed-function oxidation and alter the amount of NADPH entering Pathways I and II. It is concluded that, in general, the concept of two main pathways of NADPH utilization in the liver is valid, but that the ratios of NADPH utilization in the two pathways gives a better indication of the use of NADPH in vivo than is obtained for absolute values for the two pathways. Moreover, the centrilobular and periportal hepatocytes showed different patterns in their response to changes in dietary lipid and the administration of phenobarbitone. These results indicate the different metabolic roles that these two groups of cells may play in the metabolism of foreign compounds.

Apparent diffusion coefficient of sodium phenobarbitone in ethylcellulose microcapsules: effects of capsule size

Ethylcellulose microcapsules of sodium phenobarbitone with a thick wall were prepared and fractionated. The apparent diffusion coefficient of sodium phenobarbitone was measured for the transport of the drug from the core of microcapsules into the surrounding sink condition. The apparent diffusion coefficient decreased with decreasing capsule size. Apart from structured water in and around the capsule wall, the volume fraction of pores in the membrane has been suggested as the source of the observed trend.

Role of striatal acetylcholine and free ammmonia in the central stimulatory effects of pp'DDT in rats. Protective effects of barbiturates.

pp'DDT (600 mg/kg, orally) produced an increase in the level of free ammonia and a decrease of acetylcholine in the corpus striatum of rats. These effects were maximal 5 h after the administration of pp'DDT. The animals showed tremors after 2 h, mild or moderate convulsions after 3.5 h and severe convulsions 5 h after treatment with pp'DDT. The neurochemical changes and convulsions induced by pp'DDT were modified to different degrees by barbiturates. Phenobarbitone sodium abolished the convulsions while prominal reduced the severity of convulsions in pp'DDT treated animals. The level of striatal acetylcholine in pp'DDT-phenobarbitone treated animals was not significantly different from the control values. In prominal-pp'DDT treated animals, it was slightly but significantly reduced. Primidone neither changed the severity of convulsions nor the level of striatal acetylcholine in pp'DDT treated animals. Further barbiturates had no significant effect on the level of free ammonia in pp'DDT treated rats. The results suggest that changes in the level of acetylcholine are not the cause but an effect of pp'DDT induced stimulatory effects or convulsions, mediated through an increase in the level of free ammonia or some other mechanism.

The induction of rat hepatic microsomal xenobiotic metabolism by n-octadecyl β-(3′,5′-di- tert-butyl-4′-hydroxyphenyl)-propionate

The hepatic effects of oral administration of n-octadecyl β-(3′,5′-di- tert-butyl-4′-hydroxyphenyl)propionate (OBPP) has been studied in male and female rats. OBPP administration produced both marked liver enlargement and the induction of a number of parameters of hepatic microsomal xenobiotic metabolism, including cytochrome P-450, mixed-function oxidase enzymes and UDPglucuronosyltransferase. Histological examination of liver sections from OBPP-treated rats revealed hypertrophy of the centrilobular cells of the liver lobule, and ultrastructural studies indicated a marked proliferation of the smooth endoplasmic reticulum. Reversibility studies demonstrated that the increase in liver size and in the activities of xenobiotic-metabolizing enzymes had substantially reverted to control levels 14 days after the cessation of OBPP treatment. It is concluded that OBPP is a potent inducer of hepatic xenobiotic metabolism in the rat, with properties similar to those of sodium phenobarbitone.

Enzymic formation of dehydrogenated and hydroxylated metabolites from lysergic acid diethylamide by rat liver microsomes.

1. The metabolism of lysergic acid diethylamide (LSD) was studied using rat liver microsomes, and two minor metabolites were obtained in addition to lysergic acid ethylamide and N6-desmethyl-lysergic acid diethylamide (nor-LSD) which were reported previously. 2. One of the metabolites was identified as lysergic acid ethylvinylamide, apparently formed by dehydrogenation of a diethylamide group in the side chain at the 8-position, and the other as the phenol 13-hydroxy-LSD. 3. The formation of both lysergic acid ethylamide and lysergic acid ethylvinylamide was similarly induced by pretreatment of rats with either phenobarbitone sodium or 3-methylcholanthrene, while nor-LSD formation was induced only by phenobarbitone and that of 13-hydroxy-LSD only by methylcholanthrene.

A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants

The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety in which the illuminance and unfamiliarity of the test arena are manipulated. Acute administration of sodium phenobarbitone (25 mg/kg) was without effect. Acute administration of sodium phenobarbitone (35 mg/kg) and of meprobamate (60 mg/kg) produced sedation: both locomotor activity and social interaction were reduced. On the other hand, amphetamine sulphate (2 mg/kg) and caffeine citrate (20 mg/kg) reduced social interaction, but increased locomotor activity. Chronic administration dissociated the pattern of results produced by sodium phenobarbitone (35 mg/kg) from that produced by flurazepam (0.5 mg/kg). With chronic treatment (5 days) neither drug reduced motor activity, but whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions, i.e., when the arena was unfamiliar or brightly lit.

The metabolism of dieldrin and two of its analogues: The relationship between rates of microsomal metabolism and rates of excretion of metabolites in the male rat

Malerats receiving re-entrant bile duct cannulae were given [ 14C]-dieldrin (HEOD) and [ 14C]-HEOM (15 mg/kg of each) by intraperitoneal injection. Bile collections were made without anaesthesia and nearly all 14C excretion occurred by this route. Maximal 14C excretion rates were observed between 20 and 40 min after dosing and these were much lower for dieldrin (3.17 nmoles/kg body wt/min) than for HCE or HEOM (204 and 298 nmoles/kg body wt/min respectively). Induction of liver enzymes by treatment with sodium phenobarbitone caused a significant increase in 14C excretion in the case of dieldrin (threefold) but not in the case of HCE. The rates of 14C excretion in vivo were compared with the rates of metabolism in vitro by liver microsomes for each compound. The pattern of primary metabolism observed in vivo was similar to that found in vitro for both HCE and HEOM. Whereas HCE was metabolised predominantly by microsomal monooxygenase attack, both monooxygenase and epoxide hydratase were important in the degradation of HEOM. The rate of microsomal metabolism of HCE and HEOM by non-induced rat liver microsomes was over 100 times greater than that reported for dieldrin using induced rat liver microsomes. Using values expressed in terms of unit body weight, the maximal rates of microsomal metabolism of HCE and HEOM were 5–6 times greater than the corresponding maximal rates of biliary excretion of their metabolites in non-induced rats. HCE concentrations were measured in liver microsomes from non-induced rats dosed with the chemical. The rates of hydroxylation by liver microsomes at these concentrations were of the same order as the corresponding rates of biliary excretion for the hydroxylated metabolites. The rate of microsomal hydroxylation of HCE increased approximately seventeen-fold in terms of liver weight, after phenobarbitone induction. These results suggest that the rate of metabolism can limit the rate of excretion of dieldrin metabolites in the male rat. With HCE and HEOM, however, the maximum metabolic rate is much faster and does not apparently influence the excretion rate. There may be a ‘threshold metabolic rate’ for these highly liposoluble compounds below which the rate of excretion is limited by the rate of metabolism.

Alteration of hepatic detoxication enzyme activity by dietary arsenic trioxide

The effects of dietary arsenic trioxide (As 2O 3) on liver detoxication enzymes were studied. Enzyme activity was monitored by measuring hexobarbitone sleeping time, oxidative cleavage of O-ethyl- O-p-nitrophenyl phenylphosphonothioate (EPN) and O-demethylation of p-nitroanisole, in rats fed diets containing 0, 100, 500, 1000, 2000 or 5000 ppm As 2O 3 for 15 days. Hexobarbitone sleeping time was decreased in rats given 100 ppm As 2O 3 or more; the other enzyme responses were stimulated considerably in rats given 1000 ppm As 2O 3 and most of the rats given 2000 or 5000 ppm died. The capacity of the enzyme system to be stimulated by dietary sodium phenobarbitone was not impaired by As 2O 3.

Cytochrome P-450 distribution in rat liver and the effect of sodium phenobarbitone administration

A microspectrophotometric method for assaying cytochrome P-450 in fresh 24 μm unfixed cryostat sections of rat liver has been developed. When used to assay this cytochrome in sections of microsomal preparations it has yielded results equivalent to those obtained by the conventional spectrophotometric assay of the same preparations. Random measurements made throughout sections of liver have given mean values for cytochrome P-450 concentrations which are twice those measured in microsomes prepared from the livers of the same animals (not corrected for the yield in the homogenate). Measurements of the cytochrome P-450 content of liver cells by the microspectrophotometric method show that in liver from male Wistar rats, cells nearer to the central veins contain up to twice as much cytochrome P-450 as those nearer to the portal tract (mean cell concentrations of 26.4 (±4.4) μmol/l and 17.5 (±3.0) μmol/l respectively). In the livers from similar rats, killed at the same time, but which had received 1 mg/ml sodium phenobarbitone in their drinking water for one week, the cells near the central vein contained up to five times as much cytochrome P-450 as those near the portal tract (mean cell concentrations of 77.3 (±25.0) μmol/l and 28.3 (±9.6) μmol/l respectively). The results show a selective increase in cytochrome P-450 content by the cells in the centrilobular region after treatment with sodium phenobarbitone and a smaller increase by some of the cells in the periportal region.

The effect of prolonged sodium phenobarbitone treatment on hepatic xenobiotic metabolism and the urinary excretion of metabolites of the d-glucuronic acid pathway in the rat

Male Sprague-Dawley rats were fed a 0.1 % (w/w) sodium phenobarbitone (PB) diet for periods of 4, 12 and 24 weeks. Phenobarbitone treatment resulted in a marked increase in liver size which was accompanied by the induction of several parameters of hepatic xenobiotic metabolism including mixed function oxidase enzyme activities, UDP-glucuronyltransferase, cytochrome P450 and the microsomal protein content. In addition, treatment with the barbiturate led to the stimulation of the urinary excretion of d-glucaric acid, l-gulonic acid, free d-glucuronic acid, l-ascorbic acid and xylitol. The levels of stimulation of both the hepatic and urinary parameters remained relatively constant throughout the period of treatment. On cessation of PB treatment the parameters of hepatic xenobiotic metabolism reverted to control levels at a faster rate than the excretion of the d-glucuronic acid metabolites. The results demonstrate a correlation between the urinary excretion of metabolites of the d-glucuronic acid pathway and hepatic xenobiotic metabolizing enzyme activities during the prolonged administration of PB.

In vitro hydroxylation of diphenylhydantoin and its inhibition by other commonly used anticonvulsant drugs

Using a crude 9,000 g rat liver musomal preparation, in vitro studies were carried out on (a) the metabolism (hydroxylation) of diphenylhydantoin (DPH), (b) the effect of other commonly used anticonvulsants on this hydroxylation. DPH hydroxylation exhibited saturation kinetics at a DPH substrate concentration of approximately 10 −4 M. Mean K m and V m values for the reaction were 9.3 × 10 −5 M and 23.3 μg/m1 respectively. The linear Hill plot with an interaction coefficient of 1.0 suggests that there is no cooperativity between different DPH molecules during DPH receptor binding process. The anticonvulsants ethosuximide, sodium phenobarbitone, sodium valproate and sulthiame all exhibited inhibition of DPH hydroxylation to varying degrees. K i , inhibition constants for the four anticonvulsants were respectively 1.1 × 10 −2, 9 × 10 −4, 1.8 × 10 −2 and 8.8 × 10 −4M. Inhibition of DPH hydroxylation by sodium phenobarbitone and sulthiame was strong and competitive in nature. Ethosuximide showed a weak competitive type of inhibition and sodium valproate a weak uncompetitive type of inhibition.

The metabolic effects of sodium dichloroacetate in experimental hepatitis in the rat [proceedings

Conference Article| October 01 1977 The Metabolic Effects of Sodium Dichloroacetate in Experimental Hepatitis in the Rat GUY A. H. JOHNSON; GUY A. H. JOHNSON 1University Chemical Pathology and Human Metabolism Unit, Level D, South Laboratory and Pathology Block, General Hospital, Southampton SO 94XY, U.K. Search for other works by this author on: This Site PubMed Google Scholar K. GEORGE M. M. ALBERTI K. GEORGE M. M. ALBERTI 2University Chemical Pathology and Human Metabolism Unit, Level D, South Laboratory and Pathology Block, General Hospital, Southampton SO 94XY, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1977) 5 (5): 1387–1389. https://doi.org/10.1042/bst0051387 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation GUY A. H. JOHNSON, K. GEORGE M. M. ALBERTI; The Metabolic Effects of Sodium Dichloroacetate in Experimental Hepatitis in the Rat. Biochem Soc Trans 1 October 1977; 5 (5): 1387–1389. doi: https://doi.org/10.1042/bst0051387 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1977 Biochemical Society1977 Article PDF first page preview Close Modal You do not currently have access to this content.

The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules.

Microcapsules of sodium phenobarbitone, with a wall of ethyl cellulose, have been prepared. The size distribution was determined by use of standard sieves and the effect of coreWALL ratio noted. Release of the drug into an aqueous medium was studied. The release pattern was found to have similar characteristics to the release of a drug from an insoluble porous matrix.