DISCUSSION

All plasma-concentration determinations were done at our laboratories in Sodertalje, Sweden. Two methods were used, one a minor modification of the bromocresol purple method, the other a gas chromatographic procedure. For determination of Xylocaine, Sung and Truant earlier used another colorimetric reaction, the methyl orange method. With the above-mentioned two indicators amines form a complex which can be extracted and measured in a spectrophotometer. The bromocresol purple method was chosen because with Citanest the optical density of the complex is 30% higher than that of methyl orange. But neither method is specific. We were delighted, therefore, when Svinhufvud, Ortengren and Jacobsson evolved a method utilizing a completely different technique. As shown in Fig. 1, it is possible not only to measure the Xylocaine content by using a characteristic specific for Xylocaine (or Citanest), but to determine the two when present in a mixture. Since the samples from most patients were of sufficient volume, many of those in Dr. Scott’s and Dr. Telivuo’s series were checked by both methods and, with rare exceptions, the results were in accord. With both methods the standard deviation for single determinations was about 7% of the concentrations above 2 pg/ml. At lower concentrations the accuracy was about 5 0.2 pg/ml. Plasma levels of a drug following intramuscular or subcutaneous injection are dependent not only on the absorption rate but on the rate of elimination; that is, excretion, metabolism and, not least, distribution in the tissues. Thus it is important to compare the plasma levels of Citanest and Xylocaine after intravenous injection. Fig. 2 shows average concentrations from a cross-over study on 20 volunteers, each of whom received 200 mg of the drugs on different occasions. Actually these results were obtained in the tolerance study of which Englesson will present details in the next session. The concentrations of Citanest were at all times definitely lower than those of Xylocaine. Injection was given by automatic syringe and, only 40 seconds after its completion (that is, at 3 minutes), the difference was almost significant despite substantial inter-individual variation. the clinical significance of results of blood concentration studies :