A Pharmacokinetic/Toxicodynamic Model of Cisplatin Nephrotoxicity Using the Kidney Injury Molecule-1 Biomarker.

Cisplatin is a platinum-based chemotherapeutic that causes acute kidney injury in over 30% of patients. The aim of this study was to develop a population pharmacokinetic/toxicodynamic (PKTD) model of cisplatin-induced kidney injury that incorporated plasma total platinum and urinary kidney injury molecule-1 (KIM-1) concentrations. Cancer patients receiving their first or second round of cisplatin-containing chemotherapy (n=39) were prospectively randomized to a 5-HT antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) and had blood and urine collected over 10 days.

Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HT Antagonist Antiemetic Drugs.

Cisplatin is a platinum-based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin-containing chemotherapy (n = 33) were prospectively randomized to receive a 5-hydroxytryptamine (5-HT) antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days.

Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.

Hepatocyte hopping is the hepatocyte-to-sinusoid-to-hepatocyte shuttling that increases the efficiency of hepatic elimination of xenobiotics. This phenomenon is mediated efflux of hepatic metabolites by Mrp3 and reuptake by Oatp transporters in sequential hepatocytes until eventual biliary efflux by Mrp2. Sorafenib-glucuronide (SFB-G), the major metabolite of sorafenib (SFB), undergoes hepatocyte hopping, leading to efficient biliary elimination.

Sociodemographic and dietary predictors of maternal and placental mycoestrogen concentrations in a US pregnancy cohort.

Background: Zearalenone (ZEN) is a mycotoxin contaminating grains and processed foods. ZEN alters nuclear estrogen receptor α/β signaling earning its designation as a mycoestrogen. Experimental evidence demonstrates that mycoestrogen exposure during pregnancy is associated with altered maternal sex steroid hormones, changes in placental size, and decreases in fetal weight and length.