Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia.

Background: The high rate of cardiovascular mortality in patients with end-stage renal disease (ESRD) is a significant barrier to improved life expectancy. Unique in this population is the marked development and aggressive worsening of vascular calcification (VC). Pyrophosphate (PPi), an endogenous molecule, appears to naturally inhibit soft tissue calcification, but may be depressed in chronic kidney disease (CKD) and ESRD.

Differential enantioselectivity and product-dependent activation and inhibition in metabolism of verapamil by human CYP3As.

In vitro studies of enantioselective metabolism of R-(+)- and S-(-)verapamil (VER) were conducted using human cDNA-expressed CYP3A isoforms, CYP3A4, CYP3A5, and CYP3A7. N-dealkylated products nor-VER [2,8-bis-(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile] and D617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile] were the major metabolites for all CYP3A isoforms regardless of enantiomer. Enantioselectivity of CYP3A4 and CYP3A7 was most similar among the three isoforms.

Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans.

A pharmacokinetics and metabolism study was conducted in eight healthy human volunteers. After oral administration of [14C]eplerenone (EP) at a dose of 100 mg per person as an aqueous solution, blood, saliva, breath, urine, and fecal samples were collected at various time points. All matrices were analyzed for total radioactivity and/or for EP and its open-lactone-ring form (EPA).

Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism.

O-Glucuronidation of 5-hydroxyrofecoxib is the major biotransformation pathway of rofecoxib in human, rat, and dog. The glucuronide conjugate is also involved in the reversible metabolism of rofecoxib in rat and human. Atypical bimodal phenomena were observed in their plasma concentration-time curves with a large variability among different human subjects.

Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5.

In vitro studies were conducted to identify the major metabolites of eplerenone (EP) and the cytochrome p450 (p450) isozymes involved in its primary oxidative metabolism in humans and dogs. The major in vitro metabolites were identified as 6 beta-hydroxy EP and 21-hydroxy EP in both humans and dogs. EP was metabolized by cDNA-expressed human CYP3A4 and dog CYP3A12 but only minimally by human CYP3A5.

Interconversion pharmacokinetics of eplerenone, a selective aldosterone blocker, and its lactone-ring open form.

The interconversion pharmacokinetics of eplerenone and its lactone-ring open form, SC-70303, were examined in dogs using a stable isotope method. [13CD3]EP and SC-70303 were coadministered orally (10 mg/kg) and intravenously (5 mg/kg) as aqueous solutions under fasted conditions. After I.

Atypical dose-route-dependent food effects of eplerenone in the dog: presence of food effects following intravenous dosing and lack of food effects of following oral dosing.

This study was conducted to investigate why a food effect was observed following an intravenous dose of eplerenone (EP) in the dog, but not following oral dosing. Three female dogs were implanted with a chronic portal vein access port and received radiolabeled EP doses orally (15 mg/kg in solution) and intravenously (7.5 mg/kg via cephalic and portal veins) under fasted and fed conditions.