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Biomedical subjects

D G Bailey

Publications and source records attributed to D G Bailey.

43 records · Page 3Linked to original sources

The necessity of drug level monitoring in anticonvulsant drug therapy.

A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydantoin had levels below the therapeutic range of 10-20mug/ml. Subtherapeutic levels appear to be due to inadequate dosage adjustment. Only 25% (33) of the patients receiving phenobarbital had levels below the therapeutic range. Serum levels of diphenylhydantoin or phenobarbital could not be predicted from dosage. Most patients received two or more drugs. Over 10% of the patients had potentially toxic levels of anticonvulsant drugs. High levels of diphenylhydantoin were easily recognized clinically but high levels of phenobarbital were not.

Body Weight↗

A gas chromatographic method for measuring 6-mercaptopurine in serum.

A method is presented for the measurement of 6-mercaptopurine (6-MP) in serum. Serum samples containing the drug were treated with dithioerythritol and saturated with ammonium carbonate. 6-MP was then extracted from the serum with a mixture of isopropanol-ethyl acetate (1:1, v/v) containing 0.01% ethanethiol. The solvent was evaporated, the residue dissolved in dilute hydrocholoric acid, washed with chloroform, and extracted with ethyl acetate. 6-MP was derivatized with trimethylanilinium hydroxide and measured gas chromatographically. The sulfhydryl-protecting reagents, dithioerythritol and ethanethiol, were added to prevent the decomposition of 6-MP. The extraction and clean-up method recovered 78 +/- 2% (S.E.) of the 6-MP present. Tracer amounts of [8-14C]6-MP served as the internal standard during the extraction part of the method. Theophyline was used as the internal standard during the gas chromatographic analysis. The standard curve obtained from the gas chromatograph was linear between 0.5 and 20 mug/ml of 6-MP. Serum samples were stored in the freezer for two weeks without significant loss of drug. No interference was encountered from normal serum constituents or xanthines, such as caffeine or theophylline added to serum.

Chromatography, Gas↗

Improved method for the simultaneous determination of phenobarbital, primidone and diphenylhydantoin in patient's serum by gas-liquid chromatography.

A quantitative gas-liquid chromatographic method for the simultaneous determination of phenobarbital, primidone and diphenylhydantoin in human serum is described. A double extraction is employed to improve the removal of interfering substances. The N,N-dimethyl derivatives of the compounds are prepared by "oncolumn" methylation with 50% Methelute. Decomposition of phenobarbital to N-methyl-a-phenylbutyramide was negligible if the contact time with Methelute was less than 10 min. The drugs were stable in serum for at least two weeks. This procedure provides a rapid, sensitive, selective and accurate method for the routine determination of serum concentrations of three of the most commonly prescribed anticonvulsant drugs.

Anticonvulsants↗

Multiple hepatic excretory mechanisms for organic anions. A study with succinylsulfathiazole and taurocholate in the rat.

A study was done to investigate interactions in the biliary excretion of [14-C]succinylsulfathiazole and [3-H]taurocholate after intravenous administration of the two compounds to anesthetized rats. Either compound administered alone increased bile flow and was excreted in the bile. The simultaneous infusion of both significantly increased bile flow above the values seen when either was given alone. However, the biliary-excretion rates of both compounds and their concentrations in bile were reduced when they were administered concomitantly. The simultaneous injection of radioactive taurocholate and succinylsulfathiazole did not alter significantly the plasma concentrations of either compound or their binding to plasma proteins from the values obtained when each was given alone. These results are consistent with a concept of competition between these compounds for the same liver-to-bile transport system. They contrast with previous observations that indicated that the concomitant administration of taurocholate increased the biliary excretion of acidic compounds. In the light of this work, it might be suggested that there are more than one transport system for the biliary excretion of organic anions.

Animals↗

Pentobarbital inhibits the billiary excretion of organic acids: a study with succinysulfathiazole in the rat.

The present study was undertaken to determine whether the use of pentobarbital as an anesthetic reduces the biliary excretion of acidic drugs in rats. The drug chosen for the experiment was succinylsulfathiazole, a compound excreted unmetabolized in the bile. Animals anesthetized with urethane excreted 22.1% of the dose in the bile as compared to only 8.4% for the same time period in pentobarbital anesthetized animals. The choice of anesthetic did not affec the bile flow but did influence the bile/liver concentration gradient of succinylsulfathiazole, with the pentobarbital treated rats demonstrating a significantly lower value. Despite the higher biliary excretion of succinylsulfathiazole in the urethane treated rats, the total amount in the bile plus urine was 60% of the dose in the urethane anesthetized animals as compared with 62% in the pentobarbital treated rats. These results suggest that pentobarbital reduced the hepatic transport of succiylsulfathiazole into the bile. The question whether urethane is a preferred anesthetic for biliary excretion studies warrants further investigation.

Animals↗

Studies on the blood of a Co (a-b-) proposita and her family.

The serum of a pregnant woman whose red cells typed as Co(a-b-) contained an alloantibody that, at the time of the infants delivery, was hemolytic in vitro and had a titer of 32,000 by the antiglobulin test. This antibody, which reacted with cells of all Colton-phenotypes except the proposita's own cells, showed very weak reactions with other Co(a-b-) cells and therefore cannot be called anti-Co3. The red cells of the proposita may carry a very weak Co3 antigen. No other persons of the Co(a-b-) phenotype were found in her members, among three of the four generations tested, suggested that an inhibitor gene may be responsible for the unusual Colton phenotypes in this family. The proposita's infant required one exchange transfusion with red cells obtained from the proposita. Red cells from 40,000 donors reacted with the serum of the proposita.

Adult↗