Table I.
Data for Marketed Drugs Generated in the IPRLu Model and Included in the OPLS Model “Training set”, Mean (n = 2) Data are Displayed with the Range Quoted in Brackets
| Drug | %TDiP | %SDiP | % Dose in solution | Lung T1/2 (mins) | Recovery of total dose (%)a | Calculated LogPb |
|---|---|---|---|---|---|---|
| Indacaterol | 11 (10,11) | 12 (12) | 88 | 273 (255–291) | 91 (77–104) | 3.03 |
| Ambroxol | 38 (14–61) | 41 (18–64) | 95 | 39 (14–64) | 70 (66–74) | 2.65 |
| Formoterol Fumerate | 47 (42–52) | 47 (42–52) | 100 | 24 (22–26) | 73 (70–76) | 0.83 |
| Ipratropium Bromide | 49 (34–64) | 50c | 100 | 23 (14–32) | –1.82 | |
| Tiotropium Bromided | 61 (59–62) | 16 (15,16) | –1.76 | |||
| Amiloride | 62 (61–62) | 62 (61–62) | 100 | 8 (7–10) | 81 (76–85) | -0.5 |
| Lidocainee | 75 (64–82) | 75c | 100 | 4 (4,5) | 1.54 | |
| Zanamivirf | 100 (100–100) | 100 | 100 | 7 (5–8) | 104 (100–107) | –6.54 |
| Flunisolide | 41 (28–53) | 96 (66–126) | 42 | 15 (7–22) | 139 (135–142) | 1.56 |
| Montelukast | 67 (57–78) | 92 (78–106) | 73 | 42 (23–60) | 77 (70–85) | 8.49 |
| Fluticasone Propionate | 10 (10) | 2000c | 0.5 | 115 (98–131) | 3.72 | |
| Fluticasone Furoate | 10 (7–12) | 300c | 3.2 | 153 (112–194) | 4.13 | |
| Nedocromil | 32 (23–40) | 125 (83–166) | 24 | 32 (24–40) | 85 (79–90) | 2.5 |
| Tacrolimus (prograf) | 38 (38) | 178 (176–180) | 21 | 28 (27,28) | 5.59 | |
| Budesonide | 77 (76–79) | 551 (540–561) | 14 | 3.3 (3,4) | 84 (82–87) | 2.73 |
| Salmeterol | 15 (6–24) | 41 (16–66) | 36 | 146 (59–233) | 69 (61–76) | 3.59 |
| Salbutamol | 42 (33–51) | 77 (60–93) | 55 | 21 (13–28) | 78 (75–81) | 0.32 |
aData only available for compounds where lung analysis was carried out to confirm recovery
bCalculated using Chemaxon v5.4.1.1 (http://www.chemaxon.com/)
cSolubility in dose vehicle was determined post study on a discrete weighing of the compound
dSolubility of Tiotropium was not measured in the IPRLu model experiment, therefore it was not included in the “Training set”. Safety data sheet quotes solubility to be ~5 mg/ml in PBS (pH 7.2) https://www.caymanchem.com/msdss/15773m.pdf
eLidocaine data is from n = 4
fZanamivir dose analysis failed, expected to be fully solubilised in the dose vehicle (250 μg/ml 0.2% Tween 80 in saline) due to its zwitterionic nature. Merck Index states solubility of zanamivir to be 18 mg/ml in water