Anomalous results of studies on drug interaction in man. I. Nortriptyline and antipyrine

Conflicting results were obtained in three drug interaction experiments designed to determine in man effects of chronic nortriptyline administration on plasma antipyrine half-lives. In an apparently similar design, each experiment utilized normal volunteers whose plasma antipyrine half-lives were measured before and after chronic nortriptyline administration. The same dose of liquid nortriptyline (0.2 mg/kg p.o. t.i.d. for 8 days) was used in each experiment. All subjects in the first study prolonged their plasma antipyrine half-lives, whereas seven of nine subjects in the second study significantly shortened their plasma antipyrine half-lives. In the third experiment seven of nine subjects showed no significant change in plasma antipyrine half-life. An explanation for these conflicting results obtained in the same laboratory under apparently similar experimental conditions was sought in the nature of the volunteers and in subtle changes in such variables as differences in the batches and length of storage of liquid nortriptyline.