Abstract

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 – 360 min) to the AUC for serum (AUCserum 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 l/h and 188 ± 76 l, 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.

Author Details

Authors

• P.M. Stetina¹
• B. Madai²
• V. Kulemann¹
• W. Kirch²
• C. Joukhadar¹,³

Departments

• ¹ Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Austria,
• ² Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Germany and
• ³ Institute of Pharmacology, Medical University of Vienna, Austria

Address

Ch. Joukhadar, MD
Department of Clinical Pharmacology
Division of Clinical Pharmacokinetics
Medical University of Vienna
Währinger Gürtel 18 – 20
1090 Vienna, Austria
Email: [email protected]

Citation