In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil.

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Citation

Higashi H, Watanabe N, Tamura R, Taguchi M

In Vitro P-Glycoprotein-Mediated Transport of Tadalafil: A Comparison with Sildenafil.

Biol Pharm Bull. 2017;40(8):1314-1319. doi: 10.1248/bpb.b17-00278.

PubMed ID
28769012 [ View in PubMed
]
Abstract

Tadalafil and sildenafil are selective inhibitors of phosphodiesterase type 5, showing marked pharmacokinetic variability in patients with pulmonary arterial hypertension. It has been reported that sildenafil is a substrate for P-glycoprotein (P-gp), but whether tadalafil is a substrate for P-gp remains to be determined. The objective of the present study was to elucidate whether tadalafil is a substrate for P-gp. Transcellular transport of sildenafil and tadalafil (5 microM each) was examined using renal epithelial LLC-PK1 and P-gp-expressing LLC-GA5-COL150 cell monolayers. The efflux ratio of the basal to apical (B to A) transport of sildenafil to the A to B transport after 120-min incubation in LLC-GA5-COL150 cells (1.52) was significantly higher than that in LLC-PK1 cells (0.711). The efflux ratio of the B to A transport of tadalafil to the A to B transport after 120-min incubation in LLC-GA5-COL150 cells (10.4) was significantly higher than that in LLC-PK1 cells (1.23). In LLC-GA5-COL150 cell monolayers, the Vmax and Km values of sildenafil transport calculated from a modified Michaelis-Menten equation were 101+/-64 pmol/min/cm(2) and 112+/-47 microM, respectively. On the other hand, those of tadalafil transport were 13.6+/-4.8 pmol/min/cm(2) and 22.7+/-9.3 microM, respectively. In the presence of a P-gp inhibitor (PSC833), the B to A transport of tadalafil was decreased by 28.6% in LLC-GA5-COL150 cells, and the A to B transport of tadalafil was 6.59-fold greater than that in its absence. These results indicate that tadalafil is a substrate for P-gp.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
SildenafilP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
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