Pharmacokinetics of scopolamine in serum and subcutaneous adipose tissue in healthy volunteers
Stetina, P.M.; Madai, B.; Kulemann, V.; Kirch, W.; Joukhadar, C.
International Journal of Clinical Pharmacology and Therapeutics 43(3): 134-139
2005
ISSN/ISBN: 0946-1965 PMID: 15792397 Document Number: 588709
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. Materials and 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 (Cmax) of 6.5+/-3.9 ng/ml (data in mean +/- SD) was attained after 15 +/- 3 minutes (tmax), 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 (AUCinterstitium 0 - 360min) to the AUC for serum (AUCserum0-360 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-LIP, 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.