Kinetic Analysis of Effects of Mouth Washing on Removal of Drug Residues Following Inhalation of Fluticasone Propionate Dry Powder

Abstract

Inhaled corticosteroids are widely used for treatment of asthma, though local adverse effects, such as candidiasis and hoarseness, are often seen in patients treated with those drugs. Therefore, the Packaging Inserts enclosed with such medications recommend mouth washing after inhalation for prevention of local adverse effects. In spite of that recommendation, candidiasis has been reported by patients who washed their mouth after inhalation.1) Therefore, we carried out a series of studies to investigate the influence of different methods of mouth washing on the removal rates of inhaled corticosteroids. More than 90% of the drug was recovered by washing mouth twice, when the mouth washing procedure was gargling and rinsing for 5 s each.2) However, since no significant differences were observed among 3 methods tested in a previous study, we could not conclude which was most effective. On the other hand, a relationship was observed between the amount of drug residue removed by mouth washing and the number of times of mouth washing was employed in 2 phases. 3,4)Based on those results, we speculated that drug residue remained in different amounts in easy and difficult to remove areas following mouth washing. In the present study, we investigated the differences in removal efficiency of drug residues from both easy and difficult to remove areas using 3 different methods of mouth washing; gargling and rinsing in combination, rinsing alone, and gargling alone, using a compartment model. MATERIALS AND METHODS Compartment Model for Analysis of Removal Efficiency of Drug Residues by Mouth WashingFlutide ® (FP-DPI) 50, 100, and 200 Rotadisk ® dosages were used in the present study. In addition, we employed our previously reported experimental data in the analysis, in which 3 healthy volunteers (2 males, 1 female; mean age 38.3Ϯ9.3 years old, range 28-45 years) participated.3) In the present experiment, mouth washing was started immediately following sprinkling directly in the mouth or inhalation of 1 blister, and consisted of gargling and rinsing with water for 5 s each, then the procedures were repeated 5 times. The total volume of water used for each mouth washing was 100 ml, which was divided into 5 aliquots of 20 ml each. We also developed a compartment model, in which inhaled FP-DPI residue was distributed into 2 different areas, one from which the drug was easily removed and the other from which it was difficult to remove by mouth washing. The equations used for the model were as follows:In those, X 1 and X 2 represent the amount of drugs in areas from which drugs are easily removed and difficult to remove, respectively. X 0 , F, T, and n represent the medication dose, ratio of amount of dose removed by mouth washing to medication dose, ratio of amount of dose removed from the difficult to remove area by mouth washing to total amount of dose removed by mouth washing, and the number of times of mouth washing, respectively. Further, k 1 and k 2 represent the constants of removal efficiency of X 1 and X 2 , respectively....

Inhaler technique: facts and fantasies. A view from the Aerosol Drug Management Improvement Team (ADMIT)

“…A further study suggested that ‘throat washing’ reduced colonisation of the oropharynx with Candida species in patients inhaling fluticasone propionate using a dry powder inhaler. 36 Yokoyama et al 37 showed that different types of mouth rinsing may be important, with rinsing and gargling more effective than rinsing alone for removing oropharyngeal fluticasone propionate deposited after using a DPI. An additional potential benefit of mouth rinsing after inhaling corticosteroids might be reduced deposition in the gut and thus reduced systemic exposure.…”

Randomised, multicentre, prospective interventional study to evaluate the efficacy of immediate diet in addition to standard mouth rinsing in reducing local adverse events of inhaled corticosteroid among asthmatic patients: a pilot study

“…Previous literature proposed the pharynx and larynx regions as difficult to remove areas and that it is necessary to spend more effort (5-8 times compared to easy to remove areas) in order to remove up to 90% deposited particles. 15 Lee et al suggested to use the immediate diet method instead of mouth washing after the use of ICS. Participants were educated to have a meal within five min immediately after ICS inhalation.…”