Evaluation of rosuvastatin as an organic anion transporting polypeptide (OATP) probe substrate: in vitro transport and in vivo disposition in cynomolgus monkeys

The Journal of Pharmacology and Experimental Therapeutics
Hong ShenA David Rodrigues

Abstract

Organic anion transporting polypeptides (OATPs) mediate hepatic drug uptake and serve as the loci of drug-drug interactions (DDIs). Consequently, there is a major need to develop animal models and refine in vitro-in vivo extrapolations. Therefore, the in vivo disposition of a model OATP substrate, [(3)H]rosuvastatin (RSV), was studied in the cynomolgus monkey and reported for the first time. After monkeys had received a 3-mg/kg oral dose, mass balance was achieved after bile duct cannulation (mean total recovery of radioactivity of 103.6%). Forty-two percent of the RSV dose was recovered in urine and bile, and the elimination pathways were similar to those reported for human subjects; 61.7%, 39.0%, and 2.9% of the dose was recovered in the feces, bile, and urine, respectively. The high levels of unchanged RSV recovered in urine and bile (26% of the dose) and the relatively low levels of metabolites observed indicated that RSV was eliminated largely by excretion. Also, for the first time, the in vitro inhibitory potential of cyclosporin A (CsA) toward cynomolgus monkey OATPs and sodium-taurocholate cotransporting polypeptide was studied in vitro (primary hepatocytes and transporter-transfected cells). It is concluded that one ca...Continue Reading

References

Sep 26, 2002·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K NezasaM Koike
Oct 19, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ken-ichi NezasaMasahiro Koike
Dec 12, 2003·Clinical Therapeutics·Paul D MartinTracy Short
Apr 30, 2004·Clinical Pharmacology and Therapeutics·Dennis W SchneckAli Raza
Aug 4, 2004·Clinical Pharmacology and Therapeutics·Steven G SimonsonDennis W Schneck
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Yoshihisa ShitaraYuichi Sugiyama
May 3, 2007·Clinical Pharmacology and Therapeutics·M K PasanenM Niemi
Aug 19, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Curtis D Klaassen, Hong Lu
Feb 26, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hong LuCurtis D Klaassen
Jul 12, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Satoshi KitamuraYuichi Sugiyama
Nov 22, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Evita van de SteegAlfred H Schinkel
May 29, 2009·Clinical Pharmacology and Therapeutics·J E KeskitaloM Niemi
Sep 24, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ebba BergmanHans Lennernäs
Sep 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yoshiyuki ShirasakaIkumi Tamai
Mar 2, 2010·Nature Reviews. Drug Discovery·UNKNOWN International Transporter ConsortiumLei Zhang
Jul 1, 2011·European Journal of Drug Metabolism and Pharmacokinetics·Jin-Hua Wen, Yu-Qing Xiong
Aug 10, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tsuyoshi TakahashiToshiyuki Kume
Mar 13, 2014·British Journal of Clinical Pharmacology·Thomayant PrueksaritanontS Aubrey Stoch
Mar 29, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jae H ChangJonathan Cheong
May 24, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Laurent SalphatiNico Scheer
Dec 24, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Li WangJashvant D Unadkat

❮ Previous
Next ❯

Citations

Nov 27, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hong ShenYurong Lai
Feb 26, 2016·The Journal of Pharmacology and Experimental Therapeutics·Hong ShenYurong Lai
Apr 13, 2018·The Journal of Pharmacology and Experimental Therapeutics·Ayşe UfukAleksandra Galetin
Apr 12, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rhishikesh ThakareA David Rodrigues
Jun 9, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rachel E KosaManthena V Varma
May 4, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tom De BruynJ Brian Houston
Sep 6, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bridget L MorseYurong Lai
Sep 29, 2020·Journal of Medicinal Chemistry·David A TessManthena V S Varma

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.