Reversed-phase LC assay method for deoxycholate in influenza vaccine.

Sodium deoxycholate is used for the disruption of particles in the manufacturing of some influenza vaccines. Residual deoxycholate in inactivated vaccines is currently determined using a labour-intensive colorimetric method which lacks complete specificity. An alternative assay method for residual deoxycholate in vaccine preparations was developed using reversed-phase LC.

Metabolism and disposition of phenazopyridine in rat.

1. The blood profile, tissue distribution, biliary and urinary excretion, and metabolism of 14C-phenazopyridine (PAP) was studied in male Wistar rats. 2.

Excretion of phenazopyridine and its metabolites in the urine of humans, rats, mice, and guinea pigs.

The metabolism of the urinary tract analgesic phenazopyridine [2,6-diamino-3-(phenylazo)pyridine; PAP] was studied in the urine of humans, rats, mice, and guinea pigs. Urinary excretion was rapid in human and guinea pig, but in the rat and mouse it was slower and there was significant fecal excretion. Metabolism of PAP was extensive in all four species, and there were marked quantitative differences in the routes of metabolism.

Postabsorption antidotal effects of N-acetylcysteine on acetaminophen-induced hepatotoxicity in the mouse.

Male Swiss Webster mice, treated with N-acetylcysteine (NAC, 500 mg/kg po) 1 h following acetaminophen (NAPA, 350 mg/kg po) administration, had control levels of transaminases indicating that NAC protects against NAPA-induced hepatotoxicity by postabsorption antidotal mechanism(s). Hepatic congestion induced by NAPA was reduced by NAC. Significantly higher elimination rate constants (K) for indocyanine green (500 micrograms/kg, iv) in mice treated with NAPA and NAC (K = 0.

Isoniazid-induced hepatic steatosis in rabbits: an explanation for susceptibility and its antagonism by pyridoxine hydrochloride.

Steatosis was induced in rabbits by subacute administration of isoniazid (INH, 50 mg/kg po). Concomitant treatment with pyridoxine (vitamin B6, 25 mg/kg po) antagonized both development of the hepatic lesions and the elevation of plasma concentrations of lipids. Rabbit acetylating ability was sixfold that of male Wistar rats, a species susceptible to hepatic cell necrosis, whereas hepatic cytochrome P-450 and NADPH-cytochrome c reductase were significantly lower than that observed in control or phenobarbital-induced rats.

Effect of salicylate on the fate of [14C]sulfinpyrazone in the rat.

The effect of acetylsalicylic acid (ASA, 100 mg/kg, po) on the fate of [14C]sulfinpyrazone (50 mg/kg, ip) was studied in male Wistar rats. ASA increased the rate of elimination of [14C]sulfinpyrazone-derived radioactivity from the blood during the first 5 h following drug administration. A tissue distribution study at 4 h showed that ASA increased the concentration of radioactivity in the gastrointestinal tract (GIT) and decreased it in the blood, heart, lung, and testis.

Pathways of disposition of acetaminophen conjugates in the mouse.

After a single dose of [14C]acetaminophen (50 mg/kg) was administered orally to bile duct cannulated mice, 13.9% of the radioactivity was recovered in the bile while 41.2% was found in the urine in the first 3 h after administration.

Isoniazid metabolism in the rabbit, and the effect of rifampin pretreatment.

The metabolism of 14C-isonicotinyl hydrazide (INH) (50 mg/kg, po) was studied in male New Zealand White rabbits and the effect on INH metabolism of pretreating the rabbits for 7 days with rifampin (100 mg/kg po per day) was also studied. The 14C-labelled metabolites were separated and quantitated by TLC and the unlabelled hydrazino metabolites by GLC. Absorption and elimination of INH was rapid since the peak blood 14C level was attained by 1 hr and the T 1/2 of elimination was 2.

N-acetylcysteine-induced inhibition of gastric emptying: a mechanism affording protection to mice from the hepatotoxicity of concomitantly administered acetaminophen.

Swiss Webster male mice, 22 +/- 3 g, killed 17-18 h following the concomitant oral administration of acetaminophen (350 mg/kg) and N-acetyl-cysteine (NAC, 100-500 mg/kg, treated) had statistically significant lower plasma transaminases (GOT and GPT) than control mice (acetaminophen + water). Possible mechanisms underlying this protective effect of NAC were examined. NAC (500 mg/kg) reduced [14C]acetaminophen-derived radioactivity in the blood and tissues but increased the percentage of the dose in the gastrointestinal tract.

Biliary and urinary excretion of [14C]warfarin in rabbits.

1. The biliary and urinary excretion of racemic [14C]warfarin (1 mg/kg) was studied in male rabbits. 2.

Effect of a concomitant single dose of ethanol on the hepatotoxicity and metabolism of acetaminophen in mice.

A concomitant single dose of ethanol (1 g/kg) protected mice from hepatic injury induced by acetaminophen (250 mg/kg) as evidenced by the lowering of plasma transaminases. Pharmacokinetic studies with [14C]acetaminophen indicated that ethanol enhanced the initial blood concentrations of radiolabel and its rate of elimination. A tissue distribution study suggested that these effects were probably due to an ethanol-induced inhibition of the biliary clearance of acetaminophen from the blood.

Fate of [14C]warfarin in guinea-pigs: effect of a concomitant single dose of salicylate.

When a single dose of sodium salicylate (177.8 mg kg-1, by mouth) was given with [14C] warfarin (1 mg kg-1, i.p.

Drug interactions with isoniazid metabolism in rats.

14C-Isoniazid (20 mg/kg po or iv) was administered alone or in combination with aspirin (100 mg/kg po), rifampin (30 mg/kg po), ethambutol (100 mg/kg po), or ethanol (3 g/kg po) to rats. In another experiment, phenobarbital sodium (40 mg/kg/day ip) was administered for 3 days prior to isoniazid. Aspirin and ethanol retarted the rate of isoniazid absorption from the GI tract.

Analysis of warfarin in plasma by high-pressure liquid chromatography.

An improved high-pressure liquid chromatography method for the estimation of warfarin in plasma was developed. Plasma was acidified and extracted with ethylene dichloride spiked with methylated warfarin [3-(alpha-acetonylbenzyl)-4-methoxy-coumarin] as internal standard. The residue, redissolved in dioxane, was chromatographed on a reversed-phase column using a mobile phase of 40% dioxane in water (pH 4.

Metabolism of [14C]paracetamol and its interactions with aspitin in hamsters.

1. The metabolism of [14C]paracetamol (150 mg/kg) and its interactions with aspirin (200 mg/kg) were studied in male hamsters. 2.

High-pressure liquid chromatographic determination of acetaminophen in biological fluids.

A method for the rapid estimation of free acetaminophen in biological fluids is described. The assay involves either extraction and high-pressure liquid chromatographic analysis on a 10-mum particle-size silica gel column, using a mobile phase of 10% chloroform in tetrahydrofuran. The procedure was used to determine acetaminophen levels in urine from two healthy volunteers who ingested 650 mg of 14C-acetaminophen (20 muCi), and the accuracy of the method was compared with the carbon-14 determination.