BEMNIFOSBUVIR HAS LOW POTENTIAL TO INHIBIT P-gp, BCRP, AND OATP1B1 MEDIATED TRANSPORT
Topics in Antiviral Medicine
; 31(2):201, 2023.
Article
in English
| EMBASE | ID: covidwho-2320914
ABSTRACT
Background:
Bemnifosbuvir (BEM, AT-527) is a guanosine nucleotide prodrug candidate for the treatment of COVID-19 and chronic HCV. BEM was identified in vitro as an inhibitor of drug transporters P-glycoprotein, breast cancer resistant protein (BCRP) and organic anion transporting polypeptide 1B1 (OATP1B1). Ph 1 studies in healthy participants were conducted to assess the clinical implications of these results using digoxin (DIG) and rosuvastatin (ROSU) as P-gp and BCRP/ OATP1B1 index drugs, respectively. Method(s) Both studies employed a similar design with 2 groups of 14 healthyparticipants:
Day 1/period 1, all participants received a single dose of DIG 0.25mg or ROSU 10mg alone. In period 2, participants received DIG 0.25mg or ROSU 10mg with BEM 1100mg, simultaneously (n=14) or staggered by 2h (n=14). Serial plasma samples were collected and quantitated for DIG or ROSU concentrations. Result(s) A single dose of BEM 1100mg simultaneously administered slightly increased the Cmax of DIG (78%), yet had no effect on its AUC, consistent with the transient nature of BEM plasma PK. When dosed staggered, BEM did not affect the PK of DIG. A single dose (simultaneous or staggered) of BEM 1100mg slightly increased the plasma exposure of ROSU (20%-40%). There was no effect on vital signs, ECG, and no SAEs or drug discontinuations. Conclusion(s) A single high dose of BEM 1100mg only slightly increased the plasma exposure of the P-gp and BCRP/OATP1B1 index drugs DIG and ROSU. BEM has low potential to exhibit clinical meaningful inhibition of these transporters. No dose adjustment will be needed for drugs that are sensitive substrates of P-gp or BCRP/OAT1B1 when co-administered with BEM, staggered dosing may lessen any DDI risk.
adult; clinical article; conference abstract; controlled study; drug megadose; drug therapy; drug withdrawal; electrocardiogram; electrocardiography; female; human; human tissue; male; maximum concentration; vital sign; bemnifosbuvir; breast cancer resistance protein; digoxin; endogenous compound; multidrug resistance protein 1; rosuvastatin; solute carrier organic anion transporter 1B1
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2023
Document Type:
Article
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