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Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate.
Author(s) -
Borgstrom L.,
Nyberg L.,
Jonsson S.,
Lindberg C.,
Paulson J.
Publication year - 1989
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1989.tb05334.x
Subject(s) - bioavailability , pharmacokinetics , enantiomer , terbutaline , chemistry , absorption (acoustics) , first pass effect , oral administration , pharmacology , stereoselectivity , metabolism , reabsorption , stereochemistry , medicine , kidney , biochemistry , physics , asthma , acoustics , catalysis
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.