A5052635590- Pharmacogenetics and Drug Metabolism
- Diabetes Treatment and Management
- Diabetes Management and Research
- Pharmacology and Obesity Treatment
- Vitamin D Research Studies
- Analytical Methods in Pharmaceuticals
- Antifungal resistance and susceptibility
- Metabolism, Diabetes, and Cancer
- Pharmaceutical studies and practices
- Neuroscience of respiration and sleep
- Cancer Treatment and Pharmacology
- Hormonal Regulation and Hypertension
- Cardiac electrophysiology and arrhythmias
- Pharmacological Effects and Toxicity Studies
- Drug Transport and Resistance Mechanisms
- Statistical Methods in Clinical Trials
- Potassium and Related Disorders
- Cholesterol and Lipid Metabolism
- Biosimilars and Bioanalytical Methods
- Drug-Induced Hepatotoxicity and Protection
- Pancreatic function and diabetes
- Diabetes and associated disorders
- Nuclear Structure and Function
- Pharmacological Receptor Mechanisms and Effects
- Heart Failure Treatment and Management
Alice Springs Hospital
2016-2021
Imperial College London
2019
Leiden University Medical Center
2015
Centre for Human Drug Research
2015
Society of Anesthesia and Sleep Medicine
2014
Zero to Three
2014
Office National de l'Electricite et de l'Eau Potable
2004
Novartis (Switzerland)
1999-2003
Novartis (United States)
1999-2003
Novartis (China)
2003
Current regulatory guidances do not address specific study designs for in vitro and vivo drug-drug interaction studies. There is a common desire by authorities industry sponsors to harmonize approaches, allow better assessment of the significance findings across different studies drugs. also growing consensus standardization cytochrome P450 (P450) probe substrates, inhibitors inducers development classification systems improve communication risk health care providers patients. While existing...
A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, dosing frequency and prandial state, food consumption timing, motility on absorption posaconazole. In part 1, a single dose (SD) posaconazole (400 mg) was administered alone or an acidic beverage proton pump inhibitor (PPI), both. 2, mg twice daily 200 four times daily) for 7 days without nutritional supplement (Boost). 3, SD while were fasting before, during, after high-fat meal. 4, alone,...
Current regulatory guidances do not address specific study designs for in vitro and vivo drug-drug interaction studies. There is a common desire by authorities industry sponsors to harmonize approaches allow better assessment of the significance findings across different studies drugs. also growing consensus standardization cytochrome P450 (CYP) probe substrates, inhibitors, inducers development classification systems improve communication risk health care providers patients. While existing...
The serum vitamin D-binding protein (DBP), a member of multigene family that includes a-fetoprotein (aFP) and albumin (ALB), is expressed at high levels in the adult liver.Although several studies have demonstrated presence DBP on cell surface immunocytes cytotrophoblasts, evidence extrahepatic synthesis remains inconclusive.Using Northern blot analysis RNA from multiple rat tissues, transcripts were present expected liver.In addition, mRNA was found kidney, testis, abdominal fat, 18-day...
We studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria deficiency plasma vasopressin (AVP), which progressed severity over time. Another normal urine volumes AVP when first tested at age 3 yr, but developed severe FNDI year later. For unknown reasons, one man volume despite history past. When AVP-neurophysin-II gene was amplified sequenced, exon 2/3 normal, 7 12 clones 1...
Insulin secretion is impaired in type 2 diabetes with the early response being essentially absent. The loss of this insulin hypothesized to be important deterioration glucose tolerance. To determine whether enhancement early-phase can enhance tolerance, we administered 1) 120 mg nateglinide, an insulinotropic agent that enhances secretion; 2) 10 glyburide, which later phases or 3) placebo random order 21 subjects (14 males and 7 females; aged 59.2± 2.1 yr, x ± sem; body mass index 29.7 1.0...
Abstract This study assessed the synergistic effects of nateglinide (a nonsulfonylurea d-phenylalanine derivative) and meals on insulin secretion in 24 patients with type 2 diabetes. Oral doses 60 180 mg or 120 240 were administered to two cohorts subjects 10 min before (or fasting) three times daily for 7 days, washout intervals between treatment periods. Dose-dependent increases plasma occurred, peak effect within h after treatment. Significantly greater was observed when taken a meal...
The extent of expression the GH receptor (GHR) in human tissues is largely unknown. In some cell lines and placenta, GHR gene generates two different mRNAs by alternative splicing exon 3, one coding for a full-length (GHR + 3) other isoform that lacks 3 (GHR-3), with deletion amino acid residues 7-28. To determine distribution relative abundance its isoforms man, we studied variety obtained at autopsy reverse transcription polymerase chain reaction (PCR) amplification, using isoform-specific...
Proof of concept (POC) may be defined as the earliest point in drug development process at which weight evidence suggests that it is "reasonably likely" key attributes for success are present and causes failure absent. POC multidimensional but focused on that, if not addressed, represent a threat to project crucial areas such safety, efficacy, pharmaceutics, commercial regulatory issues. The appropriate assessed through use mathematical models by evaluating consequences advancing candidate...
Abstract Background: Opioid-induced respiratory depression is potentially lethal. GAL021 a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced in animals due to stimulatory effect on ventilation at the carotid bodies. To assess humans whether stimulates breathing established and evaluate its safety, proof-of-concept double-blind randomized controlled crossover study isohypercapnic (study 1) subsequent exploratory poikilocapnic nonrespiratory end points...
OBJECTIVE: Nateglinide, a new short-acting D-phenylalanine derivative for treating type 2 diabetes, reduces mealtime blood glucose excursions by physiologic regulation of insulin secretion. This study evaluated the pharmacokinetic and pharmacodynamic interactions nateglinide metformin in subjects with diabetes. RESEARCH DESIGN AND METHODS: A total 12 diabetic following baseline characteristics were enrolled: age, 56 +/- 13 years; BMI, 28.7 4.5 kg/m2; HbA1c, 8.4 1.3%; fasting plasma 2.8...
OBJECTIVE— This study was designed to compare the pharmacodynamic effects of single doses nateglinide (A-4166), repaglinide,and placebo on mealtime insulin secretion and glycemic control in healthy subjects. RESEARCH DESIGN AND METHODS— Fifteen volunteers participated this open-label five-period crossover study. They received 10-min preprandial 120 mg nateglinide, 0.5 or 2 repaglinide, 1 min preprandially repaglinide. Subjects each dose only once, 48 h apart. Pharmacodynamic pharmacokinetic...
Plasma vitamin D binding protein (DBP) may scavenge actin released during cell lysis. We examined the plasma disappearance and tissue appearance of 125I-DBP, 125I-G-actin, DBP-G-actin complex after their intravenous administration to rats. The DBP DBP-actin were indistinguishable, with rapid initial (t1/2 = 2.6 h) slower second 7 slopes. After 125I-G-actin (nanomole) injection, paralleled that DBP-actin. All injected was associated DBP, without evidence free actin, actin-gelsolin complexes...
Objectives: Azole antifungal agents are often coadministered with immunosuppressants to recipients of solid organ and hematopoietic stem cell transplants. Posaconazole, an extended-spectrum triazole, is inhibitor the cytochrome P450 (CYP) isoenzyme CYP3A4, sirolimus, immunosuppressant, a substrate enzyme. We evaluated effects posaconazole on sirolimus pharmacokinetics in open-label, multiperiod, drug-interaction study.Methods: Twelve healthy subjects received one dose 2 mg day 1. After...
Opioid‐induced respiratory depression (OIRD) is a serious and potentially life‐threatening complication of opioid overdose, abuse, misuse. An option to avert OIRD treat patients on strong opioids with stimulants that do not interact the system consequently compromise analgesic efficacy. The BK‐channel blocker GAL021 stimulant acting at K + ‐channels expressed type 1 carotid body cells. authors performed population pharmacokinetic‐pharmacodynamic (PKPD) analysis ability reverse...
Nateglinide (Starlix®, SDZ DJN 608 or A‐4166), a new insulinotropic agent, is intended to be administered prior meal in order improve early insulin release non‐insulin‐dependent diabetes mellitus patients. The effects of on the oral bioavailability and pharmacodynamic actions nateglinide were investigated. Twelve healthy male subjects completed this randomized, single‐dose, four‐way crossover study which each subject received 60 mg dose 10 minutes before start immediately after high‐fat...
AbstractObjective:To evaluate posaconazole pharmacokinetics in subjects with different degrees of hepatic impairment compared matched healthy subjects.Research design and methods:A total 37 were enrolled this open-label, single-dose, parallel-group study; 19 18 matching demographics. Each subject received a single 400-mg oral dose after high-fat meal. Blood samples for analysis taken up to 648 h (∼4 weeks) postdose.Results:Compared maximum plasma concentration (Cmax) values normal function,...