Mochizuki, Tatsuki published the artcileEffect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) (2022), 111(6), 1315-1323, database is CAplus and MEDLINE.
This study was designed to assess the quant. performance of endogenous biomarkers for organic anion transporting polypeptide (OATP) 1B1/1B3-mediated drug-drug interactions (DDIs). Ten healthy volunteers orally received OATP1B1/1B3 probe cocktail (0.2 mg pitavastatin, 1 mg rosuvastatin, and 2 mg valsartan) and an oral dose of cyclosporin A (CysA, 20 mg and 75 mg) separated by a 1-h interval (20 mg (-1 h), and 75 mg (-1 h)). CysA 75 mg was also given with a 3-h interval (75 mg (-3 h)) to examine the persistence of OATP1B1/1B3 inhibition. The area under the plasma concentration-time curve ratios (AUCRs) were 1.63, 3.46, and 2.38 (pitavastatin), 1.39, 2.16, and 1.81 (rosuvastatin), and 1.42, 1.77, and 1.85 (valsartan), at 20 mg, 75 mg (-1 h) and 75 mg (-3 h) of CysA, resp. CysA effect on OATP1B1/1B3 was unlikely to persist at the dose examined Among 26 putative OATP1B1/1B3 biomarkers evaluated, AUCR and maximum concentration ratio (CmaxR) of CP-I showed the highest Pearson′s correlation coefficient with CysA AUC (0.94 and 0.93, resp.). Correlation between AUCR of pitavastatin, and CmaxR or AUCR of CP-I were consistent between this study and our previous study using rifampicin as an OATP1B1/1B3 inhibitor. Nonlinear regression anal. of AUCR-1 of pitavastatin and CP-I against CysA Cmax yielded Ki,OATP1B1/1B3,app (109 ± 35 and 176 ± 42 nM, resp.), similar to the Ki,OATP1B1/1B3 estimated by our physiol.-based pharmacokinetic model anal. described previously (107 nM). The endogenous OATP1B1/1B3 biomarkers, particularly CmaxR and AUCR of CP-I, corroborates OATP1B1/1B3 inhibition and yields valuable information that improve accurate DDI predictions in drug development, and enhance our understanding of interindividual variability in the magnitude of DDIs.
Clinical Pharmacology & Therapeutics (Hoboken, NJ, United States) published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.
Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics