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Biomedical subjects

C E Cook

Publications and source records attributed to C E Cook.

At least 73 records · Page 4Linked to original sources
PubMed1980

Radioimmunoassay for terfenadine in human plasma.

A radioimmunoassay procedure was developed for the antihistamine terfenadine (alpha[4-(1,2-dimethylethyl)phenyl]-4-(hydroxydiphenylmethyl)-1-piperidinebutanol). The keto analog of terfenadine was converted to its O-carboxymethyloxime derivative, which was conjugated to bovine thyroglobulin by a mixed anhydride technique. Rabbits were immunized with the resulting conjugate, and antiserums capable of binding radiolabeled terfenadine were obtained. Tritium-labeled terfenadine was prepared by a combination of exchange and reduction with platinum oxide in the presence of tritium gas, and the procedure yielded a specific activity of 48 Ci/mmole. Plasma containing terfenadine was diluted with sodium carbonate solution and extracted with hexane, and the hexane extracts were evaporated and analyzed. The between-assay coefficient of variation on control samples ranged from 8% at 10 ng/ml to 14% at 1 ng/ml. The lower practical sensitivity limit was at least as low as 0.25 ng/ml (25 pg measured). Two metabolites of terfenadine cross-reacted 16-30% with the antiserum used. However, extraction eliminated essentially all of these compounds. Analysis of plasma samples from human subjects given terfenadine showed marked intersubject variability and low plasma levels.

Benzhydryl Compounds↗
PubMed1979

Pharmacokinetic profile of caffeine in the premature newborn infant with apnea.

The pharmacokinetic profile of caffeine was studied in 32 premature newborn infants with apnea: 12 following a single intravenous dose; 3 after a single oral dose; 7 during treatment with an initial empirical (high) maintenance dose schedule; and 10 during treatment with a revised (lower) dose schedule. Mean (+/- SE) AV d, t 1/2, ke1, and clearance following a single intravenous dose were 0.916 +/- 0.070 1/kg, 102.9 +/- 17.9 hours, 0.009 +/- 0.001/hours and 8.9 +/- 1.5 ml/kg/hour, respectively. Rapid absorption was noted with plasma concentrations of 6 to 10 mg/l achieved within 30 minutes to two hours following an oral dose of 10 mg/kg. Cpss of caffeine in infants given a high empirical dose (11.2 +/- 1.5 mg/kg/day) ranged from 22.5 to 84.2 mg/l (mean = 45.3) whereas a dose schedule based on kinetic data (2.5 mg/kg/day) yielded plasma concentrations ranging from 7.4 to 19.4 mg/l (mean = 13.7). We suggest a loading dose of 10 mg/kg intravenously or orally followed by a daily maintenance dose of 2.5 mg/kg/day administered as a single dose for the treatment and prevention of neonatal apnea.

Administration, Oral↗
PubMed1979

Synthesis of 11 beta,13 beta- and 13 beta,16 beta-propano steroids: probes of hormonal activity.

Syntheses of 11 beta,13 beta- and 13 beta,16 beta-propano derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one are described. The 13 beta,16 beta bridge was constructed by intramolecular alkylation of the C-16 enolate anion from 3-methoxy-13 beta-[3'-(tosyloxy)propyl]gona-3,5-dien-17-one, the latter being obtained via Birch reduction of both aryl groups of 17 beta-hydroxy-3-methoxy-13 beta-(3'-phenoxypropyl)gona-1,3,5(10),8-tetraene (1). The 11 beta,13 beta bridge was constructed by Prins cyclization of 17 beta-acetoxy-3-methoxy-13 beta-(3'-oxopropyl)gona-1,3,5(10),9(11)-tetraene, itself obtained via Birch reduction of only the side-chain aryl group of 1. Binding affinities of certain of these compounds and substituted 13 beta-propyl derivatives of 17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one for the uterine cytosol receptor of progesterone are reported, and the origin of the high progestational activity of norgestrel and 11 beta-substituted progestins is discussed.

Animals↗
PubMed1979

Warfarin enantiomer disposition: determination by stereoselective radioimmunoassay.

Immunoassay techniques offer promise for the selective analysis of enantiomeric substances without prior separation. In a demonstrationof this selective analysis, radioimmunoassays were developed for R- and S-warfarin. The 4'-carboxyethyl analog of R,S-warfarin was resolved and the enantiomeric acids were coupled to bovine serum albumin. Immunization of rabbits with the conjugates led to formation of antisera which selectively bound the predicted enantiomer. Cross-reactions with various metabolites of warfarin were low (0.1--4%) except for 4'-hydroxywarfarin, as were cross-reactions with the opposite enantiomer (0.3--3%). Assays were developed and used to determine enantiomer half-lives in rats dosed with racemic warfarin. Results were consistent with those found previously by administration of individual enantiomers, thus indicating the utility of the radioimmunoassay method.

Animals↗
PubMed1978

Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function.

The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.

Adult↗
PubMed1978

[Gm(28), a new allotypic marker on human IgG3: peculiar interest of its study within Negroid populations (author's transl)].

A new allotype in the Gm system (Gm(28)) was described and studied. Among Caucasoids and Mongoloids, it was found with rare exceptions, in samples containing Gm(21), segregating with Gm1,17,21 and Gm1,2,17,21 haplotypes. This new antigenic determinant was found to be of particular interest among Negroid populations in which its frequency is variable. It can be detected with all--common or uncommon--haplotypes. The degree to which it is associated with some haplotypes in different populations may prove useful in the characterization of Negroid populations. This new allotypic determinant is located on the CH3 homology region of IgG3 subclass.

Animals↗
PubMed1977

Failure of anti-gamma 3 antibodies to detect some gamma3 chains by an agglutination inhibition test.

Four of eight anti-gamma3 antibodies that detect gamma3 by double diffusion were found to test for Gm allotypes when they were used in the agglutination inhibition test. One tested for Gm (26), two for Gm (11), and one for both allotypes. So far as the present data show, the remaining four test for a gamma3 isotype in the agglutination inhibition test. We suggest that a sample that is negative by the agglutination inhibition test should be tested by double diffusion before it is concluded that the sample lacks gamma3.

Animals↗
PubMed1976

Caffeine in plasma and saliva by a radioimmunoassay procedure.

Caffeine was analyzed in human plasma and saliva by a simple, rapid, and sensitive radioimmunoassay procedure. Immunization of rabbits with an antigen prepared by coupling 7-(5-carboxypentyl)-1,3-dimethylxanthine to bovine serum albumin resulted in the formation of antibodies selective for caffeine as opposed to various mono- and dimethylxanthines, mono-, di-, and trimethyluric acids and a variety of common drugs. The radioligand used for competitive binding studies was 7-(2,3-3H2-propyl)-1,3-dimethylxanthine. The procedure permits direct analysis of caffeine in plasma or saliva without extraction. Comparison with a high pressure liquid chromatography method for the analysis of caffeine gave satisfactory results and showed no evidence for interference by metabolites. A caffeine half-life of 4.0 hours determined by the radioimmunoassay was in agreement with previous work. Comparison of human plasma and saliva levels by the radioimmunoassay procedure indicated approximately equal concentrations in the two fluids.

Adult↗
PubMed1976

Measurement of diphenylhydantoin in 0.1-ml plasma samples: gas chromatography and radioimmunoassay compared.

Concentrations of diphenylhydantoin in 364 plasma samples have been measured both by radioimmunoassay and with a recently developed gas-chromatographic method, which requires only 0.1 ml of plasma per determination. There was an excellent correlation between values obtained by the two methods (r = 0.986), and in only 11 plasma samples did the results differ by more than 20%. Of the investigated samples, 105 were obtained from uremic patients. For these, an equally good agreement was obtained between the two methods. Within-assay variance was 3.1% for the immunoassay and 3.3% for the gas-chromatographic procedure. Without automatic pipetting equipment, the radioimmunoassay procedure took twice as long as the chromatographic assay, and the cost of chemicals was considerably higher. Nevertheless, the better sensitivity of the radioimmunoassay makes it of great value, especially in children, because plasma samples of 10 to 20 mul can be used.

Child↗
PubMed1976

Theophylline radioimmunoassay: synthesis of antigen and characterization of antiserum.

Antisera to theophylline (T) have been obtained by immunizing rabbits with a conjugate of 8-(3-carboxypropyl)-1,3-dimethylxanthine and bovine serum albumin. Comparison of 50% displacement values indicated good selectivity for T vs. a number of other xanthine derivatives. An analytical procedure using this antiserum can measure 200 pg of T and direct analysis of 0.1 mug/ml in plasma or 0.02 mug/ml in saliva is feasible.

Animals↗
PubMed1975

A complex pattern of disposition of phenytoin in severe intoxication.

A 5-year-old child developed phenytoin (diphenylhydantoin, DPH) toxicity after receiving 500 mg of the drug daily for 3 weeks. Plasma, urine, and duodenal fluid were collected for assay of DPH and its metabolites. The peak plasma concentration of DPH was 108 mug/ml, and the decline in plasma level did not fit first-order kinetics. The para-hydroxy, meta-hydroxy, and dihydrodiol metabolites of DPH were measured in urine; duodenal aspirate contained both DPH and the para-hydroxy metabolite. Plasma pH may affect distribution of DPH since in vitro binding of DPH to human albumin increased as pH increased.

Child, Preschool↗
PubMed1975

Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay.

Saliva and plasma levels of phenytoin (DPH) and phenobarbital (PB) in a series of epileptic patients were compared by means of a radioimmunoassat (RIA) that required only 10 mul of saliva or plasma. There was an excellent linear relation (r = 0.98) between the logarithms of the concentrations of DPH in the two fluids. The ratio saliva/plasma was remarkably constant at 0.10 and was unaffected by varying levels of PB. The ratio was close to the fraction of DPH reported unbound in plasma at 37 degrees. PB plasma and saliva levels were also closely related (r = 0.98 for logarithm of plasma and saliva levels). This relation was nonlinear [plasma ocncentration = 4.43 X (salivary concentration)0.86], but could be approximated by the ratio plasma/saliva = 3.4. The simplicity of sample collection and the sensitivity of the RIA procedure suggest that clinical monitoring of these anticonvulsant levels may be carried out by RIA on saliva samples.

Adolescent↗
PubMed1975

Flavonoids. 8. Synthesis and antifertility and estrogen receptor binding activities of coumarins and delta3-isoflavenes.

A series of coumarins and delta3-isoflavenes was prepared. Although antifertility activity was shown by all of these compounds, the required dosage in mice varied from 13.5 mug/kg/day to 50 mg/kg/day. The most potent compounds were the 2-methyl-4-ethylisoflavenes, two of which (2a and 2b) were about equipotent with DES on a molar basis. They were followed by the 2,2-dimethylisoflavenes, the 2-unsubstituted isoflavene, and the coumarins. The most active compounds possessed an acetoxy group at C-7 and an oxygen function at C-4'. Presence of fluorine at C-4' or diethylaminoethoxy at C-M decreased the antifertility activity. The uterotropic activity followed the same trends as the antifertility activity with some evidence for the separation of the two effects in the 2,2-dimethylisoflavene series. Based on a limited study it appears that two phenolic hydroxyl groups are required for the presence of good estrogen receptor binding activity. An apparent lack of correlation between the estrogen binding activity and uterotropic or antifertility effects is probably explained by in vivo metabolism.

Animals↗
PubMed1975

Cyclamates: a review of the current position.

Cyclamates were prohibited for use as food additives in the U.S.A. and other parts of the world during 1970 because of the fears of carcinogenicity. The author reviews the evidence leading to this ban and discusses the appeal made against the decision which led to the lifting of the cyclamate restrictions in Australia in November 1974.

Animals↗