Name | Therapeutic Indication3-a | MeanPapp A→Bb | S.D. | MeanPapp B→A | S.D. | B→A/A→B Ratio | MeanPapp+ GF120918 | S.D. | B→A/A→B Ratio | Pgp Substrate | Calcein-AM Result | Calcein-AM Interaction |
---|---|---|---|---|---|---|---|---|---|---|---|---|
(nm/s) | (nm/s) | (nm/s) | (% max) | |||||||||
Antipyrine | local analgesic | 792 | 88.7 | 742 | 1.89 | 0.94 | 530 | 10.6 | 0.86 | N | 1.02 | N |
Atenolol | antihypertensive | 2.56 | 0.51 | 3.17 | 0.33 | 1.24 | 2.49 | 0.02 | 1.24 | N | −0.07 | N |
Chlorpheneramine | antihistamine | 468 | 2.46 | 436 | 2.83 | 0.93 | 443 | 18.6 | 0.94 | N | 2.36 | N |
Clonidine | antihypertensive | 529 | 39.6 | 522 | 177 | 0.99 | 533 | 36.2 | 1.05 | N | 0.63 | N |
Doxylamine | antihistamine | 359 | 11.8 | 302 | 21.9 | 0.84 | 310 | 30.4 | 0.95 | N | 5.37 | N |
Guanabenz | antihypertensive | 598 | 63.6 | 543 | 13.8 | 0.91 | 544 | 72.7 | 0.82 | N | 8.60 | N |
Guanfacine | antihypertensive | 130 | 0.94 | 159 | 2.61 | 1.23 | 127 | 14.2 | 1.21 | N | 5.05 | N |
Indomethacin | anti-inflammatory | 616 | 18.2 | 597 | 7.73 | 0.97 | 616 | 24.3 | 1.10 | N | 4.63 | N |
Lidocaine | local anesthetic | 664 | 63.5 | 551 | 5.30 | 0.83 | 555 | 52.0 | 0.85 | N | 1.70c | N |
Mannitol | diuretic | 8.29 | 0.05 | 7.33 | 0.36 | 0.88 | 7.62 | 0.47 | 1.18 | N | −0.35c | N |
Mephentermine | vasopressor | 537 | 22.3 | 468 | 15.5 | 0.87 | 518 | 8.92 | 1.15 | N | −1.43 | N |
Metoprolol | antihypertensive | 296 | 56.0 | 359 | 75.3 | 1.21 | 374 | 0.74 | 0.96 | N | 5.08 | N |
Mexilitene | antiarrythmic | 682 | 121 | 593 | 27.3 | 0.87 | 594 | 64.4 | 1.17 | N | −0.37 | N |
Oxprenolol | antihypertensive | 308 | 3.52 | 420 | 14.6 | 1.37 | 306 | 7.31 | 0.88 | N | 5.53 | N |
Pheniramine | antihistamine | 308 | 13.6 | 434 | 51.5 | 1.41 | 346 | 28.5 | 1.29 | N | 1.49 | N |
Propranolol | antihypertensive | 403 | 58.4 | 421 | 19.7 | 1.04 | 440 | 8.62 | 0.86 | N | 6.22c | N |
Sulfasalazine | anti-inflammatory bowel | 6.23 | 1.20 | 10.3 | 6.54 | 1.65 | 10.7 | 0.72 | 2.17 | N | −3.45 | N |
Warfarin | anticoagulant | 781 | 47.5 | 646 | 33.0 | 0.83 | 674 | 5.90 | 0.92 | N | 1.43 | N |
Alprenolol | antihypertensive | 461 | 14.0 | 467 | 17.4 | 1.01 | 426 | 22.8 | 0.95 | N | 15.4 | Y |
Bufuralol | antihypertensive | 641 | 151 | 500 | 76.1 | 0.78 | 484 | 33.9 | 0.94 | N | 14.3 | Y |
Clemastine fumurate | antihistamine | 331d | 20.5 | 429 | 23.5 | 1.29 | 411 | 1.17 | 0.93 | N | 28.4 | Y |
Cyclobenzaprine | muscle relaxer | 385 | 2.97 | 375 | 61.7 | 0.97 | 387 | 63.0 | 1.10 | N | 23.1 | Y |
Diphenhydramine | antihistamine | 698 | 72.1 | 637 | 10.0 | 0.91 | 639 | 28.5 | 0.82 | N | 11.1 | Y |
Doxapram | respiratory stimulant | 451 | 13.9 | 635 | 19.2 | 1.41 | 474 | 18.8 | 1.00 | N | 11.7 | Y |
Lorcainide | antiarrythmic | 448 | 7.42 | 648 | 26.9 | 1.45 | 577 | 58.4 | 1.00 | N | 16.4 | Y |
Promethazine | antihistamine | 430d | 52.5 | 548 | 32.7 | 1.27 | 580 | 7.06 | 1.53 | N | 16.3 | Y |
Acrivastine | antihistamine | 11.7 | 0.34 | 43.4 | 6.15 | 3.71 | 16.2 | 0.44 | 0.87 | Y | 3.57 | N |
Cetirizine | antihistamine | 25.1 | 3.29 | 217 | 8.11 | 8.65 | 40.0 | 3.09 | 1.15 | Y | 3.32 | N |
Cimetidine | anti-ulcerative | 3.96 | 0.69 | 18.9 | 0.68 | 4.77 | 5.15 | 0.60 | 1.25 | Y | 0.16c | N |
Famciclovir | antiviral | 71.2 | 7.51 | 226 | 17.5 | 3.17 | 119 | 13.5 | 1.36 | Y | 3.12 | N |
Indinavir | antiviral | 10.9 | 7.37 | 269 | 0.09 | 24.6 | 85.0e | 0.94 | 2.52 | Y | 1.81 | N |
Labetolol | antihypertensive | 40.9 | 31.1 | 362 | 53.4 | 8.85 | 73.7 | 4.19 | 1.05 | Y | 7.11 | N |
Neostigmine | cholinergic agent | 6.92 | 0.10 | 15.4 | 0.08 | 2.23 | 8.52 | 1.06 | 0.97 | Y | 1.91 | N |
Pirenzapine | anti-ulcerative | 1.76 | 0.01 | 6.4 | 0.43 | 3.63 | 3.16e | 0.36 | 1.68 | Y | 2.16 | N |
Trimethoprim | antibacterial | 97.8 | 2.95 | 190 | 3.96 | 1.94 | 110 | 6.85 | 1.10 | Y | 1.35c | N |
Amprenavir | antiviral | 28.8 | 1.98 | 834 | 74.4 | 29.0 | 401 | 28.7 | 1.28 | Y | 14.7 | Y |
Astemizole | antihistamine | 184f | 17.1 | 408 | 41.5 | 2.22 | 461 | 5.29 | 1.34 | Y | 71.5 | Y |
Diltiazem | anti-anginal | 430 | 13.8 | 657 | 24.7 | 1.53 | 465 | 0.64 | 0.88 | Y | 37.3c | Y |
Domperidone | antiemetic | 18.5 | 3.8 | 577 | 85.2 | 31.2 | 157 | 22.5 | 0.96 | Y | 10.4 | Y |
Loperamide | antidiarrheal | 77.7 | 2 | 773 | 33.5 | 9.94 | 456 | 20.3 | 1.08 | Y | 76.3c | Y |
Mequitazine | antihistamine | 260d | 8.91 | 731 | 90.8 | 2.81 | 462 | 18.4 | 1.28 | Y | 33.5 | Y |
Nelfinivir | antiviral | 35.3 | 9.25 | 786 | 57.5 | 22.3 | 197e | 3.87 | 1.60 | Y | 30.6c | Y |
Saquinavir | antiviral | 1.51 | 0.65 | 395d | 17.5 | 261 | 220e | 26.0 | 4.91 | Y | 35.5c | Y |
Terfenadine | antihistamine | 146f | 25.1 | 421 | 26.4 | 2.88 | 285 | 23.6 | 1.21 | Y | 100c | Y |
Verapamil | antianginal | 415 | 9.02 | 718 | 21.7 | 1.73 | 440 | 21.8 | 0.99 | Y | 56.4c | Y |
Drugs in the table are grouped by response (Y = Yes and N = No) in the Pgp efflux and calcein-AM assays as described underMaterials and Methods.
↵3-a Therapeutic Indication was taken from The Merck Index, 2001; b mass balance for drugs was > 70% excepted where noted; c data taken from Polli et al. (2001a); d mass balance for this drug was 50–70%;e since the BA/AB ratio did not collapse to ≈1.0 in the presence of GF120918, the passive permeability values are over calculated; f mass balance for this drug was 40–50%.