Human pharmacokinetics prediction with an - correction factor approach and drug-drug interaction profile of bictegravir, a potent integrase-strand transfer inhibitor component in approved biktarvy for the treatment of HIV-1 infection.

Bictegravir (BIC) is a potent small-molecule integrase strand-transfer inhibitor (INSTI) and a component of Biktarvy, a single-tablet combination regimen that is currently approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. The properties, pharmacokinetics (PK), and drug-drug interaction (DDI) profile of BIC were characterised and .BIC is a weakly acidic, ionisable, lipophilic, highly plasma protein-bound BCS class 2 molecule, which makes it difficult to predict human PK using standard methods. Its systemic plasma clearance is low, and the volume of distribution is approximately the volume of extracellular water in nonclinical species. BIC metabolism is predominantly mediated by cytochrome P450 enzyme (CYP) 3A and UDP-glucuronosyltransferase 1A1. BIC shows a low potential to perpetrate clinically meaningful DDIs known drug metabolising enzymes or transporters.The human PK of BIC was predicted using a combination of bioavailability and volume of distribution scaled from nonclinical species and a modified - correlation (IVIVC) correction for clearance. Phase 1 studies in healthy subjects largely bore out the prediction and supported the methods used. The approach presented herein could be useful for other drug molecules where standard projections are not sufficiently accurate. .