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Biomedical subjects

A Polk

Publications and source records attributed to A Polk.

8 recordsLinked to original sources
PubMed1978

GLC assay of fenclorac in human plasma.

A simple, sensitive GLC assay for fenclorac is described. Plasma proteins were precipitated with methanol, and the methanolic extract was refluxed with hydrochloric acid to form the methyl esters of fenclorac and the internal standard. The esters were purified by partitioning into benzene. Aliquots of 1 microliter of the concentrated benzene phase were injected into the gas chromatograph and quantitated by a 63Ni-electron-capture detector. Recovery of fenclorac from plasma averaged 82 +/- 1.6%.

Adult↗
PubMed1978

Pharmacokinetics and disposition of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent, in rat and monkey.

14C-Labelled 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (14C-WHR-1142A, lidamidine hydrochloride) was rapidly and quantitatively absorbed from the gastrointestinal tract of rat and monkey after a single oral dose of 5 mg/kg (base). Peak 14C levels occurred within 30 min and the radiolabel was found in both the plasma and cellular components of whole blood. The half-life of the parent compound was 30 min in rat and 1 h in the monkey. The label was essentially cleared from all tissues examined within 24 h in the rat. In both rat and monkey, the compound was extensively metabolized (greater than 90%) prior to excretion and eliminated primarily in the urine (95% of the 14C dose could be accounted for in urine within 24 h in the monkey and 65% within 24 h in the rat); about 15-20% of the dose was recovered in feces within 24 h in the rat. In rat, a significant portion of the dose was eliminated in bile, and enterohepatic recirculation of 14C excreted in bile occurred. In contrast, biliary elimination of 14C was not a major pathway in the monkey.

Amidines↗
PubMed1977

Quantitative determination of fenclorac in serum.

A spectrophotometric method for the analysis of fenclorac and its metabolite, 3-chloro-4-cyclohexylbenzeneglycolic acid, in human serum was developed. The parent compound represented at least 90% of the total species present in blood; the metabolite was present to the extent of about 10%, primarily in the elimination phase. The basic procedure consists of extraction of both compounds from serum, further extraction to remove interfering substances, alkaline conversion of fenclorac to the alpha-hydroxy acid metabolite, oxidation of this metabolite to the corresponding benzaldehyde derivative, and spectrophotometric measurement of the absorbance of the aldehyde at 252 nm. A comparison of serum concentrations obtained by this method with concentrations calculated from 14C-data following oral administration of 1-14C-fenclorac to eight normal adult volunteers indicated a 90% correlation between methodologies over a range of 1.4-25.5 microgram of fenclorac/ml of serum.

Adult↗
PubMed1976

Correlation between dissolution characteristics and absorption of methaqualone from solid dosage forms.

A methaqualone tablet in two strengths, 150 and 300 mg, was developed. The dissolution rate of an experimental formulation in pH 7.0 phosphate buffer, measured by the resin flask method, was shown to correlate with bioavailability in humans. The dissolution rate criterion was used to develop the final tablet formulation. Bioavailability of this formulation in two strengths was compared with a commercial capsule formulation and a slowly dissolving tablet formulation. Correlation between dissolution rate and bioavailability was shown in freshly prepared methaqualone tablet formulations. Bioavailability of tablets under accelerated stability testing conditions remained unaltered, whereas the dissolution rates in pH 7 phosphate buffer decreased, using the resin flask method. A rotating-flask method was developed, and dissolution in 0.1 N HCl at 2 rpm correlated with the bioavailability of both new and aged tablet formulations.

Absorption↗
PubMed1976

Blood levels in methaqualone in man following chronic therapeutic doses.

Human serum was analyzed for methaqualone (MTQ) and hydroxylated metabolites by gas liquid chromatographic (GLC), ultraviolet spectrophotometric (UV) and spectrofluorimetric (SF) procedures. Intact methaqualone was found to be the major circulating drug component after administration of multiple 300 mg daily doses over a 28-day period. Hydroxylated methaqualone metabolites, if present, were estimated to be in extremely low concentrations. After acute ingestion of large quantities of methaqualone (2.4-3.0 g), at least one methaqualone metabolite, [2-methyl-3-(2' hydroxymethylphenyl)-4(3H)-quinazolinone] was present in serum obtained from subjects with a history of chronic drug abuse.

Adult↗
PubMedDate not supplied

Comparative metabolism of fenclorac in rat, dog, monkey, and man.

Fenclorac (alpha,m-dichloro-p-cyclohexylphenylacetic acid, diethylammonium salt), a new nonsteroidal anti-inflammatory agent, was rapidly and quantitatively absorbed from the gastrointestinal tract of rat, dog, monkey, and man following oral administration of a solution of 14C-labeled compound. Radiochromatography and mass spectrometry indicated that fenclorac was the principal component in plasma during both the absorption and elimination phases in all species. Small quantities of m-chloro-p-cyclohexylphenylglycolic acid metabolite were also present. Fenclorac and metabolite were confined primarily to the plasma phase of whole blood and were extensively bound to serum albumin. The plasma elimination half-time was species-dependent and varied from 1.6 hr in the rat to 6.5 hr in the dog. The principal tissues of distribution were liver, kidney, and small intestine. There was no significant accumulation or retention of drug or metabolites in any tissue compartment. Fenclorac was completely biotransformed prior to elimination in urine and bile. The major route of elimination was renal in man and monkey, and biliary in the dog. Enterohepatic recirculation of fenclorac metabolites was shown to occur in the rat. The major urinary metabolites were hydroxycyclohexyl analogs of fenclorac and m-chloro-p-cyclohexylphenylglycolic acid. There was no difference in metabolism and biological disposition of fenclorac in normal rats and rats with adjuvant-induced polyarthritis.

Administration, Oral↗