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Biomedical subjects

J L Maddocks

Publications and source records attributed to J L Maddocks.

52 records · Page 3Linked to original sources
PubMed1979

Assay of azathioprine, 6-mercaptopurine and a novel thiopurine metabolite in human plasma.

1 A simple, specific assay for 6-mercaptopurine (6-MP) in human plasma with a sensitivity of 10 ng/ml (66 nmol/1) has been developed. 2 6-MP was extracted directly from plasma into toluene using a novel extraction procedure. This involves conversion of 6-MP into a phenyl mercury derivative by its reaction with phenyl mercuric acetate in alkaline plasma and extracting into toluene. Back-extraction of the toluene layer with 0.1N HCl regenerates 6-MP, which is then oxidised to purine-6-sulphonate and assayed fluorimetrically. 3 This assay has been modified to measure azathioprine and a new thiopurine metabolite in plasma. 4 In a kidney transplant patient given azathioprine, 50 mg i.v., conversion to 6-MP was rapid and the plasma half-life of 6-MP was 36 min. 5 These assays are suitable for studying the pharmacokinetics of azathioprine in patients with kidney transplants. The 6-MP assay should also prove useful for studying the pharmacokinetics of the drug in patients with leukaemia.

Azathioprine↗
PubMed1978

Separation of thiols as phenyl mercury derivatives by thin-layer chromatography. I. Azathioprine and 6-mercaptopurine metabolites.

A method is described for converting thiol metabolites of azathioprine and 6-mercaptopurine into phenyl mercury derivatives. Separation of these derivatives was performed by chromatography on silica thin layers and they were detected by low temperature (--196 degrees) fluorescence. The parent compounds were regenerated on the chromatogram by spraying with 2 N HC1 and these were detected by low temperature fluorescence. Mercury was also detected in spots by spraying with dithizone. The method provides a simple solution to the problem of oxidation of thiol compounds during isolation procedures.

Azathioprine↗
PubMed1975

The plasma half-life of antipyrine in chromic uraemic and normal subjects.

1. Antipyrine was given intravenously in a dose of 18 mg/kg body weight to twelve patients with chronic renal failure (plasma creatinine greater than 4.9 mg/100 ml) who were not taking drugs and twenty normal subjects. 2. Plasma antipyrine levels were measured by a specific method, the plasma half-life of the drug was determined and used as an index of drug oxidation. 3. The mean (+/- s.d) plasma antipyrine half-life in patients with chronic renal failure (7.3 +/- 2.0 h) was significantly shorter than in normal subjects (13.2 +/- 4.3 h: P less than 0.002). There was no difference in the apparent volume of distribution of antipyrine between the two groups (P greater than 0.6). 4. Pretreatment of five patients with chronic renal failure and seven normal subjects with antipyrine or phenobarbitone for weeks significantly shortened the mean plasma antipyrine half-life from 7.4 +/- 2.5 h to 5.0 +/- 1.5 h in uraemics (P less than 0.005) and from 13.2 +/- 4.5 h to 6.9 +/- 1.5 h in normal subjects (P less than 0.0025).5. These results suggest that oxidation of antipyrine by hepatic microsomal enzymes is increased in patients with chronic renal failure, but a state of maximal induction of these enzymes was not observed. The clinical implication of this finding with regard to the association between liver microsomal enzyme induction and vitamin D resistant osteomalacia is discussed.

Administration, Oral↗
PubMed1975

Absorption of ampicillin from the human lung.

The absorption of ampicillin from the lungs after intratracheal administration was studied in a healthy human. Doses of 50 mg, 250 mg, and 1,250 mg were given by intratracheal injection, and absorption of ampicillin from the lungs was assessed by measuring plasma levels, the area under the plasma level-time curve, and urinary excretion. All these indices of absorption increased with the dose of ampicillin. An intratracheal dose of 100 mg of probenecid together with 250 mg of ampicillin failed to reduce the absorption of ampicillin from the lungs. The uptake of ampicillin by human foetal bronchial slices in vitro was also studied; although viable, they did not accumulate ampicillin. These preliminary results suggest that ampicillin is absorbed from the lungs by passive diffusion.

Absorption↗
PubMed1975

Absorption of phenol red from the human lung.

Pulmonary absorption of phenol red was studied in normal subjects. Phenol red was administered by intratracheal injection and its urinary excretion was used as an index of pulmonary absorption. Doses ranging from 3 to 30 mg were given to two subjects and urinary phenol red excretion was found to be rate limited. That this effect occurred in the lung was shown by giving the dye intravenously to one subject. A linear relationship between dose and urinary excretion was then observed. Intratracheal p-aminohippurate did not reduce pulmonary absorption of phenol red in one subject. Pulmonary absorption of phenol red dissolved in 0-9% saline and 0-18% saline was compared in nine subjects. Dye absorption was three times greater when it was given in 0-18% saline. When the saline concentration of phenol red doses was held constant there was a linear relationship between the intratracheal dose and urinary excretion in one subject. These results suggest that phenol red is absorbed from the lung by passive diffusion. They also show the importance of solvent effects when studying pulmonary absorption of a substance.

Absorption↗