ABSTRACT
BACKGROUND: Patients with radiation-induced xerostomia produce little or no saliva. Several studies have demonstrated the efficacy of systemic administration of pilocarpine hydrochloride in individuals with post-radiation xerostomia. However, analysis of pilocarpine lozenges for treatment of post-radiation xerostomia in patients with head and neck cancer has not been reported. METHODS: The aim of this study was to quantify improvement in clinical symptoms and salivary function after treatment of post-radiation xerostomia with pilocarpine lozenges. In a double-blinded, placebo-controlled trial, 33 head and neck cancer patients were assigned randomly to receive Salagen tablet, pilocarpine hydrochloride lozenge (3 or 5 mg) or placebo lozenge every 10 days. At each visit, a subjective evaluation was undertaken through the use of visual analog scales before and at 180 minutes after treatment. Whole resting saliva was collected before and at 0, 30, 60, 90, 120, 150 and 180 minutes after treatment. RESULTS: The percentage of patients with decreased feeling of oral dryness, sore mouth or speaking difficulties after taking 5-mg pilocarpine lozenge was greater than Salagen or placebo. There were statistically significant increases in salivary production in pilocarpine treatment groups vs. placebo (P < 0.05). CONCLUSION: The 5-mg pilocarpine lozenge produced the best clinical results, but further investigation with a larger group of patients is required.
Subject(s)
Cranial Irradiation/adverse effects , Muscarinic Agonists/administration & dosage , Pilocarpine/administration & dosage , Xerostomia/drug therapy , Adult , Cross-Over Studies , Double-Blind Method , Female , Head and Neck Neoplasms/radiotherapy , Humans , Male , Middle Aged , Patient Satisfaction , Salivation/drug effects , Surveys and Questionnaires , Tablets , Treatment Outcome , Xerostomia/etiologyABSTRACT
Concentrations of pilocarpine in plasma, saliva and urine from three healthy male volunteers were measured using a fluorescence derivatisation method, following administration of a single 10 mg oral dose. Pharmacokinetic parameter values were estimated from concentration-time profiles. Linear correlations between plasma and saliva pilocarpine concentrations (r2=0.945, n=10, p<0.001; r2=0.954, n=12, p<0.001) and plasma concentrations and salivation rate (r2=0. 863, n=12, p<0.001; r2=0.862, n=15, p<0.001) were established. Pilocarpine and an unidentified metabolite, respectively 20.3% and 34.7% of the oral dose, were excreted into urine.
Subject(s)
Muscarinic Agonists/pharmacokinetics , Pilocarpine/pharmacokinetics , Saliva/metabolism , Adult , Area Under Curve , Biotransformation , Half-Life , Humans , Male , Middle Aged , Muscarinic Agonists/blood , Muscarinic Agonists/urine , Pilocarpine/blood , Pilocarpine/urine , Pilot Projects , Salivation/drug effectsABSTRACT
Pilocarpine is used orally to treat xerostomia but patients vary widely in their response and ability to tolerate this drug. To elucidate the potential pharmacokinetic contribution of serum to this variability, the enzymatic hydrolysis of pilocarpine in human serum in vitro was investigated using a stability indicating HPLC assay. The reaction at 37 degrees C follows Michaelis-Menten kinetics (K(m) = 2.78 +/- 0.48 mmol/liter, Vmax = 79 +/- 13 nmol min-1 ml 1; n = 5) and produces pilocarpic acid as the only detectable product. The distribution of pilocarpine esterase activity in a group of healthy young adults at age 21 (n = 163; 87 males, 76 females) was examined by incubating serum samples with pilocarpine (10 mmol/ liter) at 37 degrees C for 60 min. The distribution was positively skewed and ranged from 4 to 132 nmol min-1 ml-1 with a mean value of 55 +/- 23 nmol min-1 ml 1. The means for males and females were not significantly different. Similar measurements in xerostomia patients undergoing treatment with oral pilocarpine showed that those with higher serum esterase activity tolerated pilocarpine well and tended to require higher doses for relief of xerostomia, whereas those with low activity were sensitive to the adverse effects of the drug and were adequately treated with a lower dose. The results suggest that at least some of the variability in response to oral pilocarpine is due to differences in serum pharmacokinetics.
Subject(s)
Carboxylic Ester Hydrolases/blood , Pilocarpine/pharmacology , Adult , Female , Humans , Kidney/enzymology , Liver/enzymology , Male , Xerostomia/enzymologyABSTRACT
A sensitive assay for pilocarpine in biological fluids has been developed involving HPLC of a fluorescent derivative of 4-bromomethyl-7-methoxycoumarin. Pilosine as internal standard was added before the derivatisation step. The fluorescent derivatives were well resolved and separated from excess reagent and endogenous compounds on a cyanopropyl silica column. The detection limit of pilocarpine in biological fluids was 1.0 ng/ml and the assay was linear up to a concentration of 150 ng/ml. The assay was applied to a preliminary study of pilocarpine disposition in man after a single oral dose. This is the first report of pilocarpine excretion into saliva.
