Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyruvic Acid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,495 records · Page 83Linked to original sources
PubMed1977

Effect of thiamine deficiency in pregnant and lactating rats on the brain of their offspring.

In an attempt to create a model of human infantile beriberi, pregnant rats were fed, from the 10th day of pregnancy through lactation, a low-thiamine diet. Controls were either pair-fed or offered a nutritionally complete diet ad libitum. Dams exhibited symptoms of thiamine deficiency after 30 days on the experimental diet, whereas the their pups displayed signs of thiamine deficiency from the 14th postnatal day. Brain transketolase activity was depressed in day-old thiamine-deficient pups, and brain pyruvic acid levels were elevated after the 7th postnatal day. From the 14th postnatal day, brains of thiamine-deficient pups contained less phospholipids, cerebrosides and cholesterol than those of both controls. On the 21st day, weight and lipid content of brains of thiamine-deficient and of pair-fed pups were lower than those of normal controls. In some rats rehabilitation with thiamine was begun on the 19th day, and after 23 days, brain cerebroside content was still lower in the experimental group than in both controls. Since cerebrosides are an essential component of myelin, this finding may suggest damage of the myelin sheath.

Animals↗
PubMed1979

Effects of biguanides on the intermediate metabolism of glucose in normal and portal-strictured rats.

Phenformin and metformin treatments may be complicated by lactic adidosis. This metabolic complication seems favoured by preexistent hepatic disease. We have therefore compared the metabolic effects of phenformin and metformin on non fasting normal and portal-strictured rats. The latter group is characterized by impaired hepatic passage of these drugs without hepatocellular lesions. Given orally to normal rats over 5 days, phenformin (20 mg/kg/24 h) and metformin (150 mg/kg/24 h) decreased blood glucose levels and increased blood urea and the substrates of gluconeogenesis (alanine, glutamine, lactic and pyruvic acids), effects more apparent with phenformin than metformin. In non-treated portal strictured rats, blood glucose levels were lower and the intermediate metabolites were higher than in noraml rats, suggesting a modification of gluconeogenesis. Treatment of the portal strictured group by phenformin or metformin induced no changes in the studied parameters. This absence of effect of the biguanides in portal strictured rats supports the postulate that, in normal rats, biguanides act principally on hepatic metabolism by reducing gluconeogenesis and that, in the absence of other hepatic damage, the presence of a peri-hepatic shunt, which, by itself, modifies gluconeogenesis, does not further predispose to lactic acidosis during short term administration of biguanides.

Alanine↗
PubMed1970

Isolation and identification of new constituents in milk fat.

After removal of cholesterol on a digitonin column, the unsaponifiable matter of milk fat was examined for alcoholic substituents. Derivatization with pyruvic acid chloride 2,6-dinitrophenylhydrazone and fractionation of the derivatives gave four main fractions. The second, the hexane-benzene fraction, was shown by thin-layer chromatography to have a mobility similar to many common sterols. The hexane-benzene fraction was saponified and gave rise to free alcohols, which were then analyzed on a combination gas-liquid chromatograph-mass spectrometer. Dihydrolanosterol, previously unreported in milk fat, and lanosterol, previously identified but never confirmed, were characterized. The sterols which were precipitated on the digitonin column, were removed, and by the use of the combination gas-liquid chromatograph-mass spectrometer beta-sitosterol was identified. In addition, lanosterol and dihydrolanosterol were isolated from the unsaponifiable matter by chromatography on Florisil.

Alcohols↗
PubMed1984

Transport of 2-oxoisocaproate in isolated hepatocytes and liver mitochondria.

The transport of 2-oxoisocaproate into isolated hepatocytes and liver mitochondria of rat was studied using [U-14C]2-oxoisocaproate and the silicone oil filtration procedure. 2-Oxoisocaproate uptake by hepatocytes was composed of: rapid adsorption, unmediated diffusion and carrier-mediated transport. The carrier-mediated transport was strongly inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid and p-chloromercuribenzoate, was less sensitive to alpha-cyano-4-hydroxycinnamate and insensitive to p-chloromercuriphenylsulphonate. Other 2-oxo acids: pyruvate, 2-oxoisovalerate and 2-oxo-3-methylvalerate, were also inhibitory. The kinetic parameters of the carrier-mediated transport were Km 30.6 mM and Vmax 23.4 nmol/min per mg wet wt, at 37 degrees C. It is concluded that at its low, physiological, concentration, 2-oxoisocaproate penetrates the hepatocyte membrane mainly by unmediated diffusion. The uptake of 2-oxoisocaproate by isolated liver mitochondria was partly inhibited by alpha-cyano-4-hydroxycinnamate, the inhibitor of mitochondrial monocarboxylate carrier. The remaining uptake was linearly dependent on 2-oxoisocaproate concentration and represented unmediated diffusion. The carrier-mediated transport exhibited the following kinetic parameters: Km 0.47 mM, Vmax 1.0 nmol/min per mg protein at 6 degrees C; and Km 0.075 mM and Vmax about 8 nmol/min per mg protein at 37 degrees C.

Animals↗
PubMed2005

Biotin-rich intranuclear inclusions in morule-lacking adenocarcinoma of the gallbladder: a new category of "neoplastic/non-morular" lesions.

Biotin-rich intranuclear inclusions, also called "optically clear nuclei," are observed in various neoplastic and non-neoplastic lesions, including pregnancy-related endometrium and benign and malignant neoplasms with morular structures. A recent study reported that lesions with biotin-rich intranuclear inclusions can be classified as "(non-neoplastic) pregnancy-related endometrial" and as "(neoplastic) morular" category. In the present report, we describe two cases of well-differentiated adenocarcinoma of the gallbladder in which biotin-rich intranuclear inclusions were found without morular structures. Immunohistochemically, as reported previously, the intranuclear inclusions were positive for biotin and two biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). Intranuclear expression of beta-catenin was also observed in neoplastic cells with and without intranuclear inclusion. We also detected a frame shift mutation of APC gene in one case but no mutation of beta-catenin gene in both cases. Although intranuclear expression of beta-catenin by mutation of APC gene might contribute to carcinogenesis in our cases, the relationships among intranuclear expressions of beta-catenin, biotin, biotin-binding enzymes and intranuclear inclusions remain unclear. Our cases are the first neoplastic lesions with biotin-rich intranuclear inclusions that lacked morular structures. We propose a new "neoplastic/non-morular" category for lesions with biotin-rich intranuclear inclusions.

Adenocarcinoma↗
PubMed2003

Prokaryotic homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase in the 2-nitrobenzoate degradation pathway of Pseudomonas fluorescens strain KU-7.

The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase and 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase, respectively. The NbaC enzyme carries out the oxidation of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate-6-semialdehyde, while the NbaD enzyme catalyzes the decarboxylation of the latter compound to 2-aminomuconate-6-semialdehyde. The NbaC and NbaD proteins were overexpressed in Escherichia coli and characterized. The substrate specificity of the 23.8-kDa NbaC protein was found to be restricted to 3-hydroxyanthranilate. In E. coli, this enzyme oxidizes 3-hydroxyanthranilate with a specific activity of 8 U/mg of protein. Site-directed mutagenesis experiments revealed the essential role of two conserved histidine residues (His52 and His96) in the NbaC sequence. The NbaC activity is also dependent on the presence of Fe(2+) but is inhibited by other metal ions, such as Zn(2+), Cu(2+), and Cd(2+). The NbaD protein was overproduced as a 38.7-kDa protein, and its specific activity towards 2-amino-3-carboxymuconate-6-semialdehyde was 195 U/mg of protein. Further processing of 2-aminomuconate-6-semialdehyde to pyruvic acid and acetyl coenzyme A was predicted to proceed via the activities of NbaE, NbaF, NbaG, NbaH, NbaI, and NbaJ. The predicted amino acid sequences of these proteins are highly homologous to those of the corresponding proteins involved in the metabolism of 2-aminophenol (e.g., AmnCDEFGH in Pseudomonas sp. strain AP-3). The NbaR-encoding gene is predicted to have a regulatory function of the LysR family type. The function of the product of the small open reading frame, NbaX, like the homologous sequences in the nitrobenzene or 2-aminophenol metabolic pathway, remains elusive.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1975

Radical mechanisms for 1,5-dihydroflavin reduction of carbonyl compounds.

A discussion of the expected mechanism of radical reduction of carbonyl compounds by dihydroflavin as it relates to the structure of the carbonyl compound is provided. Factors which must be taken into account are the free energies of formation of the radical anions (CR2O), THE ACIDITY OF THE CONJUGATE ACID OF THE CARBONYL FUNCTION (R2C negative charge OH), and the stability of the carbanion species of the product [(-)CR2(OH)]. It is proposed that in those instances where the product alcohol can flavin radical to CR2O or CR2OH occurs, otherwise H transfer is the terminal step for dihydroflavin reductions. The free energy of formation of the radical species CH2OH obtained by acid-catalyzed electron transfer from dihydroflavin (Fred) to formaldehyde is shown to be less than the experimentally determined free energy of activation (increment F is not equal to exp) for the reduction of formaldehyde by dihydroflavin (i.e., Fred plus CH2O leads to Fox plus CH2OH). Therefore, the radical pair composed of dihydroflavin radical species serve as an intermediate in the reduction. Our proposed mechanism is: Fred plus CH2O ka[H3O] forms k-a[H2O] Frad CH2OH leads to kc Fox plus CH3OH. The value of kaah/k-a has been obtained from the calculated standard potential Eo' for Fred plus CH2O plus H forms Frad plus CH2OH. Assuming ka to represent a two-step process (i.e., Fred plus CH2O plus H k'a forms k'-a Fred plus CH2OH kb forms k-b Frad CH2OH, where ka equals (k'akb)/(k'-ak-b), the value of k'-a will equal 10-10 M-minus 1 sec-minus 1 and kb 10-9 M-minus 1 sec-minus 1. From k'a/k'-a and kb there can be computed the expected value of increment F is not equal to calc as a function of pH. Comparison of increment F is not equal to calc to increment F is not equal to exp reveals that increment F is not equal to calc varies from increment F is not equal to exp by only about 2kcal mol-minus 1 (8.4 kJ mol-minus 1) between pH 5 and 9. Similar considerations establish that radical intermediates should serve eminently well in dihydroflavin reduction of ethyl pyruvate, pyruvic acid, etc. In these cases, 1 e transfer should compete with H transfer to yield the carbanions as the immediate products. Similar comparisons suggest that dihydronicotinamide reduction proceeds via RPyH plus C negative charge O forms RPyH plus C-0minus +H forms -H RPyH plus C-OH forms RPy plus HC-OH.

Aldehydes↗
PubMedDate not supplied

[Pyruvate dehydrogenase deficit associated to the C515T mutation in exon 6 of the E1alpha gene].

INTRODUCTION: Pyruvate dehydrogenase (PDH) deficiency constitutes the most frequent metabolic origin of congenital lactic acidosis and is also responsible for a less usual form, found exclusively in females, which leads to a dysmorphic syndrome accompanied by severe cerebral malformations. The most common defect affects fraction E1alpha (gene Xp22.1-22.2). AIM: To report the case of a young female with PDH deficiency, dysmorphic syndrome, cerebral deformations and an unidentified mutation in the corresponding gene. CASE REPORT: An 8-month-old female with microcephaly, a narrow forehead, nasal hypoplasia, anteverted nostrils, thin lips, axial hypotonia, epileptic seizures and an umbilical hernia. Magnetic resonance imaging of the brain revealed intense supra- and infratentorial cortico-subcortical atrophy, ventricular dilatation and agenesis of the corpus callosum. Lactic and pyruvic acid concentrations were high both in blood and in cerebrospinal fluid (CSF), and the level of alanine was high in CSF. Muscular histology results were normal. PDH complex activity in fibroblasts and in muscle tissue, as well as that of the mitochondrial respiratory chain complexes in muscle homogenate, were found to be normal. A molecular genetic study of the gene for PDHE1alpha, both in formed elements in the blood and in fibroblasts, showed a C > T change in nucleotide 515 (C515T) of exon 6, which causes a P172L change in the protein. A study of 108 controls ruled out the possibility of a polymorphism. The parents did not have the mutation. CONCLUSIONS: The C515T mutation of exon 6 of the gene for PDH E1alpha is described. Normal activity of the PDH complex in fibroblasts and in muscle tissue does not exclude this condition.

Brain↗
PubMed1999

A fluorometric assay for cyclic guanosine 3',5'-monophosphate incorporating a Sep-Pak cartridge and enzymatic cycling.

We developed a sensitive and nonradioactive fluorometric assay for cyclic guanosine 3',5'-monophosphate (cGMP). Guanine nucleotides except cGMP were enzymatically phosphorylated to GTP. cGMP, absorbed into a Sep-Pak amino propyl cartridge, was eluted separately from GTP. Purified cGMP was enzymatically converted to GTP, which was applied to the GTP-GDP cycle using succinic thiokinase and pyruvate kinase. When pyruvic acid produced by the GTP-GDP cycle was reduced by lactate dehydrogenase, a reduced form of nicotinamide adenine dinucleotide (NADH) was equivalently oxidized to NAD(+). NAD(+) was further converted into fluorescent compound, which was excited at 370 nm and emitted fluorescence at 460 nm, by a strong alkali. When 20 nmol NADH was used for this assay, the calibration curve over 50 to 500 fmol cGMP became sufficiently linear. The detection limit for cGMP was ca. 5 fmol (signal to noise ratio >3). Using this assay, we confirmed that the cGMP content in the left atrial strip of dog was changed from 11.4 +/- 3.8 to 19.3 +/- 2.6 fmol/mg wet wt of tissue (mean +/- SE, n = 6) by electrical driving at 1 Hz. Carbachol (1 microM) further increased the cGMP to 45.6 +/- 9.2 fmol/mg wet wt of tissue. From these results, it is suggested that this novel assay for cGMP is highly sensitive and can be applied to various biological samples.

Animals↗
PubMed1999

Synergetic activation of outwardly rectifying Cl- currents by hypotonic stress and external Ca2+ in murine osteoclasts.

1. An outwardly rectifying Cl- (ORCl) current of murine osteoclasts was activated by hypotonic stimulation. The current was characterized by rapid activation, little inactivation, strong outward rectification, blockage by DIDS and permeability to organic acids (pyruvate and glutamate). 2. The hypotonically activated ORCl current was inhibited by intracellular dialysis with an ATP-free pipette solution, but not by replacement of ATP with a poorly hydrolysable ATP analogue adenosine 5'-O-(3-thiotriphosphate). The current amplitude was reduced when intracellular alkalinity increased over the pH range 6.6-8.0. 3. Intracellular application of cytochalasin D occasionally activated the ORCl current without hypotonic stress, but inhibited activation of the ORCl current by hypotonic stimulation. The hypotonically activated ORCl current was unaffected by a non-actin-depolymerizing cytochalasin, chaetoglobosin C, but partially inhibited by deoxyribonuclease I. 4. Removal of extracellular Ca2+ inhibited activation of the ORCl current by hypotonic shock, but did not reduce the current once activated. The hypotonically activated ORCl current was partially decreased by intracellular dialysis with 20 mM EGTA. 5. With 10 mM Ca2+ in the extracellular medium, the ORCl current was activated in response to more minor decreases in osmolarity than with 1 mM Ca2+. The increased sensitivity to hypotonicity was mimicked by increasing the intracellular Ca2+ level (pCa 6.5). 6. These results suggest that hypotonic stimulation and a rise in the extracellular Ca2+ level synergistically activate the ORCl channel of murine osteoclasts, and that the activating process is modified by multiple intracellular factors (pH, ATP and actin cytoskeletal organization).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

13C nuclear magnetic resonance evidence for gamma-aminobutyric acid formation via pyruvate carboxylase in rat brain: a metabolic basis for compartmentation.

The compartmentation of amino acid metabolism is an active and important area of brain research. 13C labeling and 13C nuclear magnetic resonance (NMR) are powerful tools for studying metabolic pathways, because information about the metabolic histories of metabolites can be determined from the appearance and position of the label in products. We have used 13C labeling and 13C NMR in order to investigate the metabolic history of gamma-aminobutyric acid (GABA) and glutamate in rat brain. [1-13C]Glucose was infused into anesthetized rats and the 13C labeling patterns in GABA and glutamate examined in brain tissue extracts obtained at various times after infusion of the label. Five minutes after infusion, most of the 13C label in glutamate appeared at the C4 position; at later times, label was also present at C2 and C3. This 13C labeling pattern occurs when [1-13C]glucose is metabolized to pyruvate by glycolysis and enters the pool of tricarboxylic acid (TCA) intermediates via pyruvate dehydrogenase. The label exchanges into glutamate from the TCA cycle pool through glutamate transaminases or dehydrogenase. After 30 min of infusion, approximately 10% of the total 13C in brain extracts appeared in GABA, primarily (greater than 80%) at the amino carbon (C4), indicating that the GABA detected is labeled through pyruvate carboxylase. The different labeling patterns observed for glutamate and GABA show that the large detectable glutamate pool does not serve as the precursor to GABA. Our NMR data support previous experiments suggesting compartmentation of metabolism in brain, and further demonstrate that GABA is formed from a pool of TCA cycle intermediates derived from an anaplerotic pathway involving pyruvate carboxylase.

Animals↗
PubMed1975

Conversion of nitrosobenzene to N-phenylacetohydroxamic acid by yeast pyruvate decarboxylase.

In the presence of yeast enzyme concentrate or purified yeast pyruvate decarboxylase, nitrosobenzene was converted in part to N-phenylacetohydroxamic acid. This transformation had to be catalyzed by the enzyme, since the incubation of nitrosobenzene with the cofactor of pyruvate decarboxylase did not produce the hydroxamic acid. Similar incubations conducted with phenylhydroxylamine did not yield any detectable amounts of N-phenylacetohydroxamic acid.

Carboxy-Lyases↗
PubMed1999

Modelling of factor Xa-inhibitor complexes: a computational flexible docking approach.

In order to understand the structural basis of Factor Xa (FXa) specificity, structural complexes of FXa with its synthetic inhibitors are determined using a computational docking approach. The AutoDock suite of programs is used to determine the binding modes of the synthetic inhibitors such as 3- and 4-amidinobenzylphenyl ether (ABP), amidinophenyl pyruvic acid (APPA), diamidinobenzofuranyl ethene (DABE), and DX-9065a 2-(5'-amidino-2'-benzofuranyl)-3-(7'amidino-2'-napthyl)-propionic acid (ABAP) to FXa. The synthetic inhibitors docked in the present study are different in size, nature of linkage, and properties. Two sets of simulations were carried out for synthetic inhibitors docking to FXa. In the first set of simulations, no explicit water molecules were included. In the second set of simulations two explicit solvent molecules were considered. In all the computationally predicted synthetic inhibitor complexes of FXa, the specificity pocket residue Asp-189 is involved in hydrogen bonding with the bound inhibitor. The active site water molecule WAT522 is involved in hydrogen bonding with all the bound inhibitors. The computed energies clearly discriminate the high affinity from low affinity binders.

Amidines↗
PubMed1978

Anticonvulsant activity and inhibition of respiration in rat brain homogenates by substituted trimethoxybenzamides.

Ten N-[4-[4-(arylthiosemicarbazido)carbonyl]phenyl]-3,4,5-trimethoxybenzamides were synthesized and characterized by their sharp melting points, elemental analyses, and IR and NMR spectra. All substituted benzamides were evaluated for their anticonvulsant activity. The degree of protection afforded by these compounds (100 mg/kg ip) against pentylenetetrazol (90 mg/kg sc)-induced convulsions in mice ranged from 10 to 80%. The ability of substituted benzamides to inhibit respiratory activity was observed by inhibition of oxidation of pyruvate, alpha-ketoglutarate, NADH, and succinate by rat brain homogenates. Inhibition of pyruvic acid oxidation was concentration dependent. The anticonvulsant activity of substituted benzamides was not related to their ability to inhibit cellular respiratory activity.

Animals↗
PubMed1979

High-pressure liquid chromatographic assay for hydralazine in human plasma.

A specific high-performance liquid chromatographic assay for hydralazine in human plasma was developed. Plasma hydralazine is reacted with 10 microliter of p-anisaldehyde for 7 min at room temperature to form hydralazine p-anisaldehyde hydrazone. This derivative is extracted into ethyl acetate, and the solvent is removed by evaporation. The residue is reconstituted in 100 microliter of methanol, and 90 microliter is injected onto a reversed-phase column. The mobile phase is 32% acetonitrile in 0.75 M acetate buffer, pH 3.4, at a flow rate of 2 ml/min. The retention time of hydralazine p-anisaldehyde hydrazone is 6.5 min. The average coefficient of variation over 10-200 ng/ml is 5.5%, and the sensitivity limit is 5 ng/ml. Under the assay conditions, hydralazine pyruvic acid hydrazone, a known plasma metabolite of hydralazine, yields less than 0.1% hydralazine. Detectable plasma hydralazine levels of 5-20 ng/ml were found 10-30 min after a 0.5-mg/kg oral dose of hydralazine hydrochloride was given to a male volunteer.

Adult↗
PubMed1979

High-performance liquid chromatographic studies of reaction of hydralazine with biogenic aldehydes and ketones.

To understand hydrazone formation in hydralazine metabolism, the reaction of hydralazine with various biogenic aldehydes and ketones (acetone, pyruvic acid, acetoacetic acid, formaldehyde, and acetaldehyde) in pH 7.4 buffer was studied for potential alterations in hydralazine pharmacokinetics secondary to alcoholism and diabetes. The corresponding hydrazones were isolated, and their structures were characterized. High-performance liquid chromatography was used to monitor the reactions. An aqueous solvent reversed-phase liquid chromatographic system was used to separate hydralazine and its derivatives. Reaction of hydralazine with formaldehyde or acetaldehyde produced the corresponding hydrazones. Formation of an s-triazolo ring system yielded the known s-triazolo[3,4-alpha]phthalazine and 3-methyl-s-triazolo[3,4-alpha]phthalazine metabolites, which also were isolated and characterized and suggested nonenzymatic metabolism.

Aldehydes↗
PubMed1983

Determination of hydralazine in human whole blood.

The time required for the separation of plasma from the cellular components of blood can permit the in vitro loss of hydralazine. Thus, a high-performance liquid chromatographic (HPLC) procedure for the measurement of hydralazine in blood has been developed. 4-Methylhydralazine was used as an internal standard. The addition of p-anisaldehyde led to the formation of the p-anisaldehyde hydrazones of hydralazine and the internal standard. HPLC on a reverse-phase cyano column provided an analytical procedure in which the average relative standard deviation over the concentration range of 1-160 ng/ml was 8.3%. Hydralazine pyruvic acid hydrazone, a known circulating metabolite of hydralazine, yielded only 0.05 mole % hydralazine when submitted to this assay procedure.

Chromatography, High Pressure Liquid↗
PubMed1988

Relative bioavailability of immediate- and sustained-release hydralazine formulations.

The in vivo performance of hydralazine sustained-release dosage forms prepared using an ethylcellulose-coated drug:resin complex was studied in healthy males who were determined to be slow acetylators. Two studies were performed. The first study (I) compared four different coating levels (6.8, 8.7, 10, and 12%) with an immediate-release tablet and a solution. The second study (II) compared three additional coating levels (4, 5, and 7.8%) to the 6.8% formulation from the first study. Both hydralazine peak blood concentration (Cmax) and area under the blood concentration-time curves (AUC) decreased as the coating level increased [coating level (Cmax, ng/mL; AUC, ng.h/mL): 4% (37; 58), 5% (31; 55), 6.8% (13; 42 and 14; 39); 7.8% (16; 38), 8.7% (11; 34), 10% (7.8; 21), 12% (8.9; 17)]. In Study I both the solution and the immediate-release tablet were administered in two divided doses at 8 a.m. (fasting) and 2 p.m. (post-prandial). There was evidence for decreased bioavailability of unchanged hydralazine after the 2 p.m. doses as compared with the 8 a.m. doses. On the other hand, an assay that measures primarily the pyruvic acid conjugate of hydralazine yielded much higher concentrations after the afternoon dose. The results of these studies indicate that a sustained-release dosage form of hydralazine can be prepared using an ethyl-cellulose coated drug:resin complex and its in vivo characteristics are related to the coating level. Hydralazine bioavailability is influenced by food or recent prior exposure to hydralazine.

Adult↗