Assessment of the relationship between plasma nortriptyline concentration and inhibition of salivation: Single-dose study

In order to evaluate the relationship between plasma nortriptyline concentration and anticholinergic effect, a single blind cross-over study of nortriptyline was performed. Seventeen healthy male volunteers were given single doses of nortriptyline (25, 50, and 75 mg) and placebo in a cross-over manner. Plasma nortriptyline concentration was measured by high performance liquid chromatography and spontaneous salivation flow was measured. Peak plasma levels of nortriptyline were attained at about 5 hours after drug administration. The corresponding area under the plasma concentration time curve (AUC) from zero-time to 12 hours after the respective dose of 25 mg, 50 mg and 75 mg nortriptyline were 87.1 ± 32.8 ng ml^-1·h (n = 7), 231.2 ± 61.3 ng ml^-1·h (n = 5) and 293.0 ± 83.9 ng ml^-1·h (n = 5), respectively. Saliva flow significantly decreased in all dose groups when compared with placebo. The percentage inhibitions of salivation at each indicated dose were 24.2 ± 12.1% (25 mg), 38.3 ± 13.2% (50 mg) and 51.9 ± 10.3% (75 mg). The inhibition of salivation showed highest correlation with log cumulative plasma levels of nortriptyline. The twelve hour plasma AUC which showed 50% inhibition of salivation was 338.7 ng ml^-1·h.