Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance.

Steady-state population pharmacokinetics of a noncommercial immediate-release metformin (hydrochloride) drug product were characterized in 28 severely obese children with insulin resistance. The concentration-time profiles with double peaks were well described by a 1-compartment model with 2 absorption sites. Mean population apparent clearance (CL/F) was 68.

The role of mitochondrial bioenergetics and reactive oxygen species in coronary collateral growth.

Coronary collateral growth is a process involving coordination between growth factors expressed in response to ischemia and mechanical forces. Underlying this response is proliferation of vascular smooth muscle and endothelial cells, resulting in an enlargement in the caliber of arterial-arterial anastomoses, i.e.

Mitochondrial oxidative stress corrupts coronary collateral growth by activating adenosine monophosphate activated kinase-α signaling.

Objective: Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart.

Approach And Results: Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth.

Associations of ABCB1 and IL-10 genetic polymorphisms with sirolimus-induced dyslipidemia in renal transplant recipients.

Background: Hyperlipidemia is a common adverse effect of sirolimus (SRL). We previously showed significant associations of ABCB1 3435C>T and IL-10 -1082G>A with log-transformed SRL dose-adjusted weighted-normalized trough. We further examined to see whether these polymorphisms were also associated with SRL-induced dyslipidemia.

Diabetes mellitus reduces the clearance of atorvastatin lactone: results of a population pharmacokinetic analysis in renal transplant recipients and in vitro studies using human liver microsomes.

Background And Objective: Patients with diabetes mellitus might be at a higher risk of HMG-CoA reductase inhibitor (statin)-induced myotoxicity, possibly because of reduced clearance of the statin lactone. The present study was designed to investigate the effect of diabetes on the biotransformation of atorvastatin acid, both in vivo in nondiabetic and diabetic renal transplant recipients, and in vitro in human liver samples from nondiabetic and diabetic donors.

Subjects And Methods: A total of 312 plasma concentrations of atorvastatin acid and atorvastatin lactone, from 20 nondiabetic and 32 diabetic renal transplant recipients, were included in the analysis.

Associations of ABCB1 3435C>T and IL-10-1082G>A polymorphisms with long-term sirolimus dose requirements in renal transplant patients.

Backgrounds: Sirolimus (SRL) absorption and metabolism are affected by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) 1236C>T, 2677 G>T/A, and 3435C>T, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) -392A>G, cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5) 6986A>G and 14690G>A, interleukin (IL)-10 -1082G>A, and tumor necrosis factor (TNF) -308G>A polymorphisms with SRL dose-adjusted, weight-normalized trough concentrations (C/D) at 7 days, and at 1, 3, 6, and 12 months after initiation of SRL.

Methods: Genotypes for 86 renal transplant patients who received SRL-based maintenance immunosuppressive therapy were determined using polymerase chain reaction followed by chip-based mass spectrometry.

Morphine and its metabolites after patient-controlled analgesia: considerations for respiratory depression.

Study Objective: To assess concentrations of morphine and its metabolites after patient-controlled analgesia (PCA).

Design: Pilot pharmacokinetic study of morphine and pharmacokinetic simulation.

Setting: Post-anesthesia care room and ward of an academic teaching hospital.

Population pharmacokinetics of mycophenolic acid and metabolites in patients with glomerulonephritis.

Mycophenolic acid (MPA) is an inosine monophosphate dehydrogenase inhibitor used for glomerulonephritis treatment. The objective of the current study was to develop a population pharmacokinetic model for MPA and metabolites in glomerulonephritis to enable appropriate design of MPA regimens in these patients with alterations in kidney structure and function. Thirty-nine patients with glomerulonephritis and receiving mycophenolate mofetil were recruited to participate in a 24-hour pharmacokinetic study.

Pharmacokinetic-pharmacodynamic modeling of the hypotensive effect of remifentanil in infants undergoing cranioplasty.

Objectives: Although remifentanil has been used to induce hypotension during surgery in infants, no pharmacokinetic-pharmacodynamic (PKPD) model exists for its quantitative analysis. Our aim was to determine the quantitative relationship between whole blood remifentanil concentration and its hypotensive effect during surgery in infants.

Methods/materials: We studied seven infants (age 0.

Population pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery.

Background: The aim of this study was to provide a model-based analysis of the pharmacokinetics of remifentanil in infants and children undergoing cardiac surgery with cardiopulmonary bypass (CPB).

Methods: We studied nine patients aged 0.5 to 4 years who received a continuous remifentanil infusion via a computer-controlled infusion pump during cardiac surgery with mildly hypothermic CPB were studied.

Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children.

Objectives: Propofol is a sedative-hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration-response relationship during EGD in children.

Population pharmacokinetics of mycophenolic acid and its 2 glucuronidated metabolites in kidney transplant recipients.

The population pharmacokinetics of mycophenolic acid (MPA) and its phenolic (MPAG) and acyl (AcMPAG) glucuronide metabolites were studied in patients taking enteric-coated mycophenolate sodium. Plasma samples (n = 232), obtained from 18 renal transplant recipients, were analyzed for MPA, MPAG, and AcMPAG using a validated high-performance liquid chromatography/ultraviolet assay. Population pharmacokinetic analysis was performed using NONMEM.

Population pharmacokinetics of tacrolimus in whole blood and plasma in asian liver transplant patients.

Objectives: The objectives of this study were to develop population pharmacokinetic models of tacrolimus in an Asian population with whole blood and plasma drug concentration data, to compare the variability of the pharmacokinetic parameters in these two matrices and to search for the main patient characteristics that explain the variability in pharmacokinetic parameters.

Study Design: Prospective pharmacokinetic assessment followed by model fitting.

Patients: Whole blood samples from 31 liver transplant patients in a local hospital receiving oral tacrolimus as part of their immunosuppressive therapy were assessed.