Bioequivalence Studies of Sildenafil Citrate Orodispersible Film Administered with and without Water vs ViagraⓇ Film-Coated Tablets in Healthy Male Volunteers.

Background: Orodispersible film (ODF) formulation offers ease of use, convenience of administration, and other advantages, especially for patients who have difficulty in swallowing or are on liquid restriction compared with conventional oral formulations for the treatment of erectile dysfunction. Objectives: These studies compared the bioequivalence of 50 mg sildenafil citrate ODF formulation (test drug) with the marketed 50 mg sildenafil citrate film-coated tablet (FCT) (ViagraⓇ; Pfizer, New York, NY) (reference drug), with and without water in 2 randomized cross-over studies. Methods: Two randomized cross-over studies were conducted. The first study explored the bioequivalence of test drug administered with and without water compared with the reference drug with water. The second study investigated the bioequivalence of test drug, without water, compared with the reference drug with water. Forty-two and 80 healthy male volunteers were recruited in the first and second study, respectively. All volunteers fasted for 10 hours pre-dose. A 1-day washout period between doses was observed. Blood samples were collected at both before (up to 120 minutes before dosing) and after dosing (at different intervals up to 14 hours) stages. Statistical analyses on pharmacokinetic parameters were performed. Safety and tolerability for both the formulations were evaluated. Results: In the first study, bioequivalence was demonstrated for sildenafil citrate ODF administered with water when compared with the ViagraⓇ FCT. The ratios of adjusted geometric means (90% confidence interval (CI)) were maximum plasma concentration: 1.02 (94.91-108.78) and area under the plasma concentration-time curve: 1.09 (104.49-113.21) for sildenafil citrate ODF administered with water vs ViagraⓇ FCT. These ratios were within the bioequivalence acceptance range of 80% to 125%, indicating that the bioequivalence criteria were met. The pharmacokinetic parameters for the second study also showed bioequivalence for sildenafil citrate ODF (without water) compared with ViagraⓇ FCT. The ratios of adjusted geometric means (90% CI) were maximum plasma concentration: 1.02 (95.47-109.36) and area under the plasma concentration-time curve: 1.06 (103.42-108.40) for sildenafil citrate ODF administered without water vs ViagraⓇ FCT. Adverse events in both the studies occurred at similar rates for the 2 formulations and were mild in intensity. Conclusions: These results suggest that the new ODF formulation can be used interchangeably with the marketed FCT formulation. Sildenafil citrate ODF administered with and without water met bioequivalence criteria compared with ViagraⓇ FCT administered with water under fasted conditions in healthy adult male volunteers. The new ODF formulation can be used as a suitable alternative to the conventional oral solid dosage form.

The Comparative Bioavailability of Fluticasone and Azelastine Delivered as a Single Fixed Dose Combination (MP-AzeFlu) in Comparison to Two Different Formulations of Azelastine and Fluticasone Propionate Following Intranasal Administration in Healthy Chinese Volunteers.

Objective: Two studies (Study I and Study II) were conducted in healthy Chinese volunteers to confirm that there was no pharmacokinetic drug interaction between AZE and FLU in MP-AzeFlu. The secondary objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components. Methods: Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William's design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC0-tlast, AUC0-∞ and Cmax were analyzed. Results: The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 100.29% (94.31-106.66%), 100.76% (94.60-107.32%) and 93.14% (81.47-106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC0-tlast, AUC 0-∞ and Cmax were 83.48% (69.81-99.82%), 100.19% (87.34-114.94%) and 81.91% (68.50-97.95%). Conclusion: The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects.

Limits of longitudinal decline for the interpretation of annual changes in FEV1 in individuals.

OBJECTIVE: Spirometry-based screening programmes often conduct annual assessment of longitudinal changes in forced expiratory volume in 1 second (FEV1) to identify individuals with excessive rates of decline. Both the American Thoracic Society (ATS) and the American College of Occupational and Environmental Medicine (ACOEM) recommend a reference limit value of > or =15% for excessive annual decline. Neither the ATS nor the ACOEM adjust this limit for the precision of the existing spirometry data. The authors propose an improved method of defining the reference limit of longitudinal annual FEV1 decline (LLD) based on the precision of the spirometry data. METHOD: The authors used data from four monitoring programmes and measured their data precision using a pair-wise within-person variation statistic. They then derived programme- and gender-specific absolute and relative LLD values and validated these against the 95th percentiles for observed yearly changes in FEV1. RESULTS: The relative limit for annual decline was more practical than the absolute limit as it adjusted for gender differences in the magnitude of FEV1. The programme-specific relative limit values were in good agreement with 95th percentiles for year-to-year FEV1 changes and ranged from 6.6% to 15.8%. For individuals with COPD and bronchial hyperreactivity the 95th percentiles for year-to-year changes were about 15% and higher. CONCLUSIONS: The relative longitudinal limit for annual FEV1 decline based upon precision of measurements is valid and can be generalised to different gender and population groups. A relative limit of approximately 10% appears appropriate for good quality workplace monitoring programmes, whereas a limit of about 15% appears appropriate for clinical evaluation of individuals with an obstructive airway disease. Computer software based on the method described is available from the corresponding author.

Spirometry Longitudinal Data Analysis Software (SPIROLA) for Analysis of Spirometry Data in Workplace Prevention or COPD Treatment.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality. Periodic spirometry is often recommended for individuals with potential occupational exposure to respiratory hazards and in medical treatment of respiratory disease, to prevent COPD or improve treatment outcome. To achieve the full potential of spirometry monitoring in preserving lung function, it is important to maintain acceptable precision of the longitudinal measurements, apply interpretive strategies that identify individuals with abnormal test results or excessive loss of lung function in a timely manner, and use the results for intervention on respiratory disease prevention or treatment modification. We describe novel, easy-to-use visual and analytical software, Spirometry Longitudinal Data Analysis software (SPIROLA), designed to assist healthcare providers in the above aspects of spirometry monitoring. Software application in ongoing workplace spirometry-based medical monitoring programs helped to identify increased spirometry data variability due to deteriorating test quality and subsequent improvement following interventions, and helped to enhance identification of individuals with excessive decline in lung function.