Table 3

Transport and calcein-AM results for non-CNS-indicated drugs

NameTherapeutic Indication3-aMeanPapp A→BbS.D.MeanPapp B→AS.D.B→A/A→B RatioMeanPapp+ GF120918S.D.B→A/A→B RatioPgp SubstrateCalcein-AM ResultCalcein-AM Interaction
(nm/s) (nm/s) (nm/s) (% max)
Antipyrinelocal analgesic79288.77421.890.9453010.60.86N1.02N
Atenololantihypertensive2.560.513.170.331.242.490.021.24N−0.07N
Chlorpheneramineantihistamine4682.464362.830.9344318.60.94N2.36N
Clonidineantihypertensive52939.65221770.9953336.21.05N0.63N
Doxylamineantihistamine35911.830221.90.8431030.40.95N5.37N
Guanabenzantihypertensive59863.654313.80.9154472.70.82N8.60N
Guanfacineantihypertensive1300.941592.611.2312714.21.21N5.05N
Indomethacinanti-inflammatory61618.25977.730.9761624.31.10N4.63N
Lidocainelocal anesthetic66463.55515.300.8355552.00.85N1.70c N
Mannitoldiuretic8.290.057.330.360.887.620.471.18N−0.35c N
Mephenterminevasopressor53722.346815.50.875188.921.15N−1.43N
Metoprololantihypertensive29656.035975.31.213740.740.96N5.08N
Mexiliteneantiarrythmic68212159327.30.8759464.41.17N−0.37N
Oxprenololantihypertensive3083.5242014.61.373067.310.88N5.53N
Pheniramineantihistamine30813.643451.51.4134628.51.29N1.49N
Propranololantihypertensive40358.442119.71.044408.620.86N6.22c N
Sulfasalazineanti-inflammatory bowel6.231.2010.36.541.6510.70.722.17N−3.45N
Warfarinanticoagulant78147.564633.00.836745.900.92N1.43N
Alprenololantihypertensive46114.046717.41.0142622.80.95N15.4Y
Bufuralolantihypertensive64115150076.10.7848433.90.94N14.3Y
Clemastine fumurateantihistamine331d 20.542923.51.294111.170.93N28.4Y
Cyclobenzaprinemuscle relaxer3852.9737561.70.9738763.01.10N23.1Y
Diphenhydramineantihistamine69872.163710.00.9163928.50.82N11.1Y
Doxapramrespiratory stimulant45113.963519.21.4147418.81.00N11.7Y
Lorcainideantiarrythmic4487.4264826.91.4557758.41.00N16.4Y
Promethazineantihistamine430d 52.554832.71.275807.061.53N16.3Y
Acrivastineantihistamine11.70.3443.46.153.7116.20.440.87Y3.57N
Cetirizineantihistamine25.13.292178.118.6540.03.091.15Y3.32N
Cimetidineanti-ulcerative3.960.6918.90.684.775.150.601.25Y0.16c N
Famciclovirantiviral71.27.5122617.53.1711913.51.36Y3.12N
Indinavirantiviral10.97.372690.0924.685.0e 0.942.52Y1.81N
Labetololantihypertensive40.931.136253.48.8573.74.191.05Y7.11N
Neostigminecholinergic agent6.920.1015.40.082.238.521.060.97Y1.91N
Pirenzapineanti-ulcerative1.760.016.40.433.633.16e 0.361.68Y2.16N
Trimethoprimantibacterial97.82.951903.961.941106.851.10Y1.35c N
Amprenavirantiviral28.81.9883474.429.040128.71.28Y14.7Y
Astemizoleantihistamine184f 17.140841.52.224615.291.34Y71.5Y
Diltiazemanti-anginal43013.865724.71.534650.640.88Y37.3c Y
Domperidoneantiemetic18.53.857785.231.215722.50.96Y10.4Y
Loperamideantidiarrheal77.7277333.59.9445620.31.08Y76.3c Y
Mequitazineantihistamine260d 8.9173190.82.8146218.41.28Y33.5Y
Nelfinivirantiviral35.39.2578657.522.3197e 3.871.60Y30.6c Y
Saquinavirantiviral1.510.65395d 17.5261220e 26.04.91Y35.5c Y
Terfenadineantihistamine146f 25.142126.42.8828523.61.21Y100c Y
Verapamilantianginal4159.0271821.71.7344021.80.99Y56.4c 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%.