Salivary Flow Rates and Pharmacokinetics in Healthy Japanese and Caucasian Volunteers Administered Oral Pilocarpine

Abstract

Salivary insufficiency and the resultant xerosfunction caused by radiotherapy of head and neck tomia are consequences of tissue damage from cancer. In multicentre, randomised, placeboradiotherapy used in the management of head and controlled trials, pilocarpine at a dose of 5mg has neck cancer[1,2] and from Sjogren’s syndrome, an been demonstrated to provide individuals with sigautoimmune disease in which lymphocytic innificant relief of the symptoms of xerostomia and filtrates destroy moisture-producing exocrine with significant increases in salivary flow with little glands.[3] Consequences of xerostomia include oral toxicity.[4-7] Use of this drug for the treatment of discomfort, difficulty in eating and swallowing solid xerostomia is under development in Japan. food and speaking without the additional aid of The principal pathway for metabolism of pilocarwater, problems with phonation, and detrimental pine, hydrolysis to pilocarpic acid,[8] has not been effects to the oral cavity, including dental caries and shown to be affected by genetic polymorphism. tooth loss as well as difficulty in wearing dentures. However, Aromdee et al.[9] recently reported that in These events result in a significant decrease in qualihumans up to 35% of orally administered pilocarty of life and marked impairment in the activities of pine may undergo oxidation, a pathway more likely daily living for these patients. to exhibit genetic polymorphism and therefore more Oral pilocarpine (Salagen® tablets; MGI likely to vary by ethnicity. Theoretically, the reportPHARMA, Inc., Bloomington, MN)1 is a muscarined variability in response to pilocarpine in the generic cholinergic agonist that is widely used in many al population may be due, in part, to genetic differcountries in the treatment of dry mouth symptoms ences in metabolism of the drug. To date, most due to Sjogren’s syndrome and salivary gland dyspilocarpine study populations have had little ethnic