Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate.
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.
Borgström
L
L
Pharmacokinetics Laboratory, AB Draco, Lund, Sweden.
Nyberg
L
L
Jönsson
S
S
Lindberg
C
C
Paulson
J
J
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013237:Stereoisomerism; D013726:Terbutaline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D013726:Terbutaline