Abstract
To determine the free concentration of a drug (propranolol) in the interstitial space in humans in vivo, seven male students were investigated by microdialysis of the periumbilical subcutaneous tissue. The microdialysis catheters were calibrated in vivo and the propranolol concentration was determined by high-performance liquid chromatography. Ten hours after intake of 80 mg of propranolol, the total plasma and free interstitial propranolol concentrations were 80±43 and 7±2 n M, respectively. After a second dose, maximum concentration was reached after 80±10 min and 98±12 min, in plasma, and the concentrations in the interstitial water were 594±138 and 27±7 n M, respectively. In a second study, microdialysis was performed on the left ventricular wall in six pigs receiving an intravenous injection of 5 mg of propanolol followed by a constant propranolol infusion for 40 min (5 mg propranolol per h). The maximum concentrations of propranolol were 97±29 and 6±2 n M in plasma and in interstitial water, respectively. The data suggest that microdialysis is a useful tool for recording the free concentrations of a drug in the interstitial space.
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