Pharmacokinetics and Pharmacodynamics of Lasix

basis of the newer data found with the radiochemical method. Figure 1 shows the serum concentrations in the usual logarithmic scale of micrograms per millilitre, the time in hours after medication and the means and the standard errors derived after intravenous application of the drug were identical with those obtained utilising the fluorimetric assay method. We were thus working well above the detection limit of that method and so there were no problems in the interpretation of the pharmacokinetic data. However, in the oral studies the serum concentrations were close to the detection limit of the fluorimetric method. We thus had to revise our findings on the I SHO ULD like to speak to you today about some of the studies that wehave performed in the last few years in the Department of Clinical Pharmacology of Farbwerke Hoechst, Frankfurt, in close co-operation with the Department of Clinical Nephrology at the University of Wtlrtzburg. Professor Dollery has recently published an article entitled 'Pharmacokinetics-master or servant?' and the answer was that pharmacokinetics is the 'servant' (Dollery, 1973). I am hoping to show you that pharmacokinetics is not an esoteric hobby for vague mathematicians who are interested in medical problems, but thatpharmacokineticsmay be the servant of practical therapeutics. When pharmacokinetic studies are performed, pharmacodynamic studies should be done simultaneously, and the aim of this should be to show a correlation between pharmacokinetic data and pharmacodynamic findings. We have studied the pharmacokinetics and pharmacodynamics of frusemide in normal subjects with doses of 40 mg orally and intravenously. In addition, we have studied the effects of high doses of frusemide (250 mg up to 1000mg) in patients with a severely impaired renal function. These were patients who were being maintained on a haemodialysis programme with inulin clearances below 10 mljmin (Rupp, Hajdu, 1970; Rupp et ai., 1970; Rupp, Zapf, 1973). One of the main problems in pharmacokinetics is the method of detection, and pharmacokinetic analysis depends largely on the sensitivity of the method. Six years ago we used for our studies on frusemide a fluorimetric method with a sensitivity limit of 0.1 ILgjml (Hajdu, Haussler, 1964). Now we have repeated these studies by means of a sulphur-35 labelled compound with a detection limit which is lower than the earlier method (Rupp, Zapf, 1973).Using this method, we found that the pharmacokinetic data