Pharmacokinetics of scopolamine in serum and subcutaneous adipose tissue in healthy volunteers.
OBJECTIVE
The objective was to develop a microdialysis set-up to measure the concentration-time course of scopolamine in the interstitium of subcutaneous adipose tissue.


METHODS
Six healthy male volunteers were eligible for data analysis. Subjects received 0.5 mg scopolamine as a 15-minute intravenous infusion. Microdialysis samples from interstitial space fluid of subcutaneous adipose tissue and blood samples were taken at predefined intervals over a period of 360 minutes. Scopolamine concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS).


RESULTS
High inter-individual variability was observed in all pharmacokinetic parameters. The mean peak serum concentration (C(max)) of 6.5 +/- 3.9 ng/ml (data in mean +/- SD) was attained after 15 +/- 3 minutes (t(max)), whereas in dialysate, a mean peak concentration of 2.7 +/- 1.7 ng/ml was measured after 27 +/- 8 minutes. The ratio of the area under the concentration versus time curve from 0-360 min for interstitium (AUC(interstitium 0-360 min0) to the AUC for serum (AUC(serum 0-360 min)) was 0.96 +/- 0.7. The elimination half-life of scopolamine was 121 +/- 85 minutes in serum and 166 +/- 117 minutes in dialysate. Values for total clearance and volume of distribution in serum were 99.1 +/- 35.0 1/h and 188 +/- 76 1, respectively.


CONCLUSIONS
In the present study, we were able to define a microdialysis set-up, which allows for the measurement of scopolamine concentrations in target tissues. In addition, we demonstrated that the concentrations of scopolamine in subcutaneous adipose tissue resemble closely the concentration-time course in serum of healthy volunteers.
Stetina
P M
PM
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria.
Madai
B
B
Kulemann
V
V
Kirch
W
W
Joukhadar
C
C
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D019540:Area Under Curve; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D018727:Muscarinic Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D012601:Scopolamine / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D018727:Muscarinic Antagonists; D012601:Scopolamine