Alma Rossabela Setyanisa, Yunias Setiawati, Irwanto Irwanto, Izzatul Fithriyah, Satria Arief Prabowo
Relationship between Parenting Style and Risk of Attention Deficit Hyperactivity Disorder in Elementary School Children
The Malaysian journal of medical sciences : MJMS
role transporters drug clearance widely acknowledged directly indirectly facilitating tissueenzyme exposure latter transporters also affect volume distribution drugdrug interactions ddis involving organic anion transporting polypeptides oatps 1b11b3 slco1b1 pharmacogenetics lead altered pharmacokinetics oatp1b substrates however several factors may confound direct interpretation pharmacokinetic parameters clinical studies using noncompartmental analysis nca review clinical data herein indicates single dose oatp1b inhibitor rifampin almost never leads increased substrate halflife often decrease clinical oatp1b substrates cyp3a4 substrates andor undergo enterohepatic cycling ehc using hypothetically simple oatp1b substrate physiologicallybased pharmacokinetic pbpk models simulated effect rifampin differed specific oatp1b inhibition due short rifampin halflife causing dissipation oatp1b inhibition time combined cyp3a4 induction calculated using simulated tissue data volume distribution indeed decreased oatp1b inhibition expectedly limited contribution liver volume however apparent counterintuitive effect rifampin volume greater clearance resulted cyp3a4 substrates using nca effect oatp1b inhibition rifampin oatp1b substrate models incorporating ehc renal clearance distinct compared simpler models using pbpk models incorporating reversible lactone metabolism clinical oatp1b substrates atorvastatin pitavastatin ddis reporting decreased halflife rifampin reproduced simulations provide explanation distinct change oatp1b substrate pharmacokinetics observed clinical studies including changes volume distribution additional mechanisms significance statement transporters involved drug clearance volume distribution distinct changes oatp1b substrate pharmacokinetics observed oatp1b inhibitor rifampin using hypothetical validated pbpk models simulations address limitations singledose rifampin complicated clinical oatp1b substrate disposition evaluating pharmacokinetic parameters oatp1b substrates rifampin ddis models account change volume distribution identify additional mechanisms underlying apparent pharmacokinetic changes oatp1b ddis