The absolute bioavailability of glyceryl trinitrate from a transdermal therapeutic system (Nitroderm TTS, 20 cm2) was assessed with a new method in 6 healthy volunteers. Instead of measuring plasma concentrations the pharmacological effects of glyceryl trinitrate were followed by digital plethysmography. Each experiment consisted of the establishment of an intravenous dose response curve which was followed by a 1-hour application of the transdermal system and a second intravenous dose response curve. The investigations were repeated after pretreatment of each subject with 0.4 mg pindolol i.v. The results show a satisfactory overall consistency of the data and indicate a release rate of 4.4 +/- SD 1.7 micrograms/min of bioavailable glyceryl trinitrate during the first hour of application of this transdermal system. This corresponds to 75 +/- 29% of the release rate obtained by analysis of residual amounts in the TTS.

In view of the use of an electronically processed digital plethysmography as a noninvasive pharmacological tool - particularly to measure effects of organic nitrates - 9 healthy young volunteers were examined. The purpose of the investigation was to study baseline recordings and to assess the effects of several well defined exogenous influences. The electronic processor calculated the D/H-ratio of each plethysmographic pulse wave, where D represents the depth of the dicrotic minimum measured from the apex of the systolic maximum and H the total hight of the plethysmographic wave. The D/H-ratio was not significantly influenced by a hot beverage, but fell after a cold drink. In undisturbed volunteers the D/H-ratio had a tendency to fall slightly during a 3-h period of observation. This tendency could be eliminated by small doses of pindolol or dihydroergotamine, but individual fluctuations of the curves were still visible. It appears therefore that a fully automated evaluation of plethysmographic recordings yields best results if the findings in a group of volunteers are averaged.