Biomedical subjects
Publications and source records attributed to S Jönsson.
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(R,S)-Bambuterol was isolated from plasma and urine by solid-phase extraction and analysed as its trimethylsilyl derivative by gas chromatography/chemical ionization mass spectrometry with ammonia as the reagent gas. Deuterium-labelled bambuterol was used as internal standard. An esterase inhibitor was added to plasma to prevent hydrolysis of bambuterol in the plasma sample. Bambuterol could be measured in plasma down to 1 nmol l-1 with a within-day variation of less than 5% (coefficient of variation). The lower limit of measurement in urine was judged to be 8 nmol l-1, a concentration at which the within-day variation was 5.4% (coefficient of variation).
1. The pharmacokinetics of the two enantiomers of terbutaline, (+)T and (-)T, and the racemate (+/-)T, have been evaluated after single intravenous and oral dosage to six healthy volunteers. 2. The mean systemic clearance, CL, was 0.19 and 0.13 l h-1 kg-1 for (+)T and (-)T, respectively. This difference was statistically significant. The mean clearance of (+/-)T was 0.20 l h-1 kg-1. Volumes of distribution were similar (1.9 l kg-1) after the three intravenous administrations. The differences in CL were reflected in values of the elimination half-life and MRT. 3. The difference in CL of the isomers could be explained by a corresponding difference in their renal clearance, CLR. Competition for stereoselective active reabsorption in the tubule might explain why (+)T seemed to enhance the CLR of (-)T when the drug was given as the racemate. 4. Oral bioavailability, calculated from plasma data, of (+)T was 7.5% and that of (-)T was 14.8%. This difference was statistically significant and was mainly due to a difference in absorption of (+)T and (-)T, but also to a difference in their subsequent first-pass metabolism. The bioavailability of (+/-)T was similar to that of (-)T. 5. (-)T appears to govern the absorption properties of the racemate, while (+)T determines its elimination behaviour. Systemic metabolism of the two enantiomers was similar and, therefore, a greater first-pass metabolism of (+)T would reflect a higher capacity of the gut wall to metabolise this isomer.
An equimolar mixture of terbutaline and [2H6]terbutaline was given as an oral solution to six healthy volunteers (three men and three women). Frequent blood samples were collected during a 24-h period and the plasma concentrations of unlabeled and deuterium-labeled terbutaline were measured by GC-MS. The overall geometric mean plasma concentration ratio of terbutaline to [2H6]terbutaline (isotope ratio) was 1.04 and differed significantly from unity. The difference can be explained by a difference in lipophilicity between the analogues, affecting their absorption. No trend in isotope ratio over the experimental time was observed. For unknown reasons, the isotope ratio was higher for women (1.07) than for men (1.00). Deuterium-labeled terbutaline can be used, intravenously or orally, as an absolute reference in bioavailability studies on terbutaline. If deuterium-labeled terbutaline is given orally in a single-day relative bioavailability study, a correlation should be made for the observed isotope effect.
The concentrations of chlorpromazine and some of its metabolites in blood plasma and CSF from chlorpromazine-treated schizophrenics with different therapeutic results were studied. Compared to a good responder a poor responder showed very high levels of the inactive metabolite chlorpromazine sulphoxide in the CSF.
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