A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials and Sample Preparation
2.2. Study Design and Population
2.2.1. Stage I—Pulmonary Administration of TFF TAC-LAC Colloidal Dispersion via a Vibrating Mesh Nebulizer
2.2.2. Stage II—Pulmonary Administration of TFF TAC-LAC Inhalable Powder via a DPI
2.3. Exposures, Covariates and Outcomes
2.3.1. Outcomes
2.3.2. Ascertainment of Other Covariates
2.4. Statistical Analysis
3. Results
3.1. Pulmonary Administration of TFF LAC-LAC Colloidal Dispersion via a Nebulizer
3.2. Pulmonary Admistration of TFF LAC-LAC Inhalable Powder via A DPI
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Lab Parameter | Pre-Inhalation (N = 20) | 24 h Post-Inhalation (N = 20) |
---|---|---|
Hemoglobin (Hgb) g/dL | 13.5 ± 1.5 | 13.4 ± 1.5 |
White Blood Cell (WBC) × 109/L | 6.0 ± 1.9 | 6.2 ± 1.4 |
Potassium mEq/L | 3.8 ± 0.3 | 3.9 ± 0.2 |
Blood Urea Nitrogen (BUN) mg/dL | 11.7 ± 3.1 | 11.0 ± 3.1 |
Creatinine mg/dL | 0.76 ± 0.18 | 0.78 ± 0.22 |
Aspartate Aminotransferase (AST) IU | 25.2 ± 19.5 | 31.1 ± 8.3 |
Variable | Pre-Inhalation (N = 20) | 1 h Post-Inhalation (N = 20) | 24 h Post-Inhalation (N = 10) |
---|---|---|---|
FEV1 (L) | 3.34 ± 0.69 | 3.31 ± 0.71 | 3.31 ± 0.80 |
FVC (L) | 4.16 ± 0.83 | 4.08 ± 0.82 | 4.09 ± 0.92 |
Ratio | 0.80 ± 0.06 | 0.81 ± 0.06 | 0.81 ± 0.06 |
FEF 25–75% (L/sec) | 3.23 ± 1.13 | 3.33 ± 1.08 | 3.29 ± 1.21 |
Symptoms | % Number of Patients (N = 20) |
---|---|
1 h following inhalation | |
• Cough | 5 (1) |
• Shortness of breath | 5 (1) |
• Abnormal throat sensation | 15 (3) |
24 h following inhalation | |
• Abnormal taste | 20 (16) |
48 h following inhalation | |
• Abnormal taste and throat sensation | 0 (0) |
Lab Parameter | Pre-Inhalation (N = 10) | 24-h Post-Inhalation (N = 10) |
---|---|---|
Hemoglobin (Hgb) g/dL | 13.4 ± 1.6 | 13.5 ± 1.5 |
White Blood Cell (WBC) × 109/L | 6.2 ± 1.9 | 6.5 ± 1.4 |
Potassium mEq/L | 4.0 ± 0.3 | 3.9 ± 0.2 |
Blood Urea Nitrogen (BUN) mg/dL | 10.7 ± 3.2 | 11.0 ± 3.1 |
Creatinine mg/dL | 0.71 ± 0.17 | 0.74 ± 0.21 |
Aspartate Aminotransferase (AST) IU | 25.6 ± 10.5 | 29.1 ± 8.3 |
Alanine Aminotransferase (ALT) IU | 24.5 ± 10.2 | 25.4 ± 10.6 |
Alkaline Phosphatase IU | 65.4 ± 18.4 | 64.5 ± 16.3 |
Variable | Pre-Inhalation (N = 10) | 1 h Post-Inhalation (N = 10) | 24 h Post-Inhalation (N = 10) |
---|---|---|---|
FEV1 (L) | 3.36 ± 0.70 | 3.35 ± 0.79 | 3.37 ± 0.81 |
FVC (L) | 4.16 ± 0.83 | 4.18 ± 0.80 | 4.08 ± 0.90 |
Ratio | 0.8 1± 0.06 | 0.80 ± 0.05 | 0.82 ± 0.06 |
FEF 25–75% (L/sec) | 3.30 ± 1.16 | 3.31 ± 1.09 | 3.30 ± 1.19 |
Symptoms | % Number of Patients (N = 10) |
---|---|
During inhalation | |
• Cough | 80 (8) |
• Throat irritation | 30 (3) |
• Distate | 80 (8) |
1 h following inhalation | |
• Cough (mild) | 90 (9) |
• Distaste (mild) | 100 (10) |
24 and 48 h following inhalation | 0 (0) |
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Sahakijpijarn, S.; Beg, M.; Levine, S.M.; Peters, J.I.; Williams, R.O., III. A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects. Pharmaceutics 2021, 13, 717. https://doi.org/10.3390/pharmaceutics13050717
Sahakijpijarn S, Beg M, Levine SM, Peters JI, Williams RO III. A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects. Pharmaceutics. 2021; 13(5):717. https://doi.org/10.3390/pharmaceutics13050717
Chicago/Turabian StyleSahakijpijarn, Sawittree, Moeezullah Beg, Stephanie M. Levine, Jay I. Peters, and Robert O. Williams, III. 2021. "A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects" Pharmaceutics 13, no. 5: 717. https://doi.org/10.3390/pharmaceutics13050717
APA StyleSahakijpijarn, S., Beg, M., Levine, S. M., Peters, J. I., & Williams, R. O., III. (2021). A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects. Pharmaceutics, 13(5), 717. https://doi.org/10.3390/pharmaceutics13050717