Aims To evaluate apixaban single dose safety, tolerability, pharmacokinetics and pharmacodynamics assess the effect of food on pharmacokinetics. Methods A double‐blind, placebo‐controlled, ascending‐dose, first‐in‐human study assessed in healthy subjects randomized to oral ( n = 43; 0.5–2.5 mg as solution or 5–50 tablets) placebo 14) under fasted conditions. An open label, randomized, two treatment crossover investigated pharmacokinetics/pharmacodynamics 21) administered 10 fed states. Both...

Four randomized, placebo-controlled, crossover studies were conducted among 282 healthy subjects to investigate whether an interaction exists between clopidogrel (300-mg loading dose/75-mg/day maintenance dose) and the proton-pump inhibitor (PPI) omeprazole (80 mg) when they are administered simultaneously (study 1); interaction, if any, can be mitigated by administering 12 h apart 2) or increasing 600-mg loading/150-mg/day dosing 3); applies equally PPI pantoprazole 4). Relative levels...

Aim Apixaban is an oral factor X a inhibitor approved for stroke prevention in atrial fibrillation and thromboprophylaxis patients who have undergone elective hip or knee replacement surgery under development treatment of venous thromboembolism. This study examined the safety, pharmacokinetics pharmacodynamics multiple dose apixaban. Method double‐blind, randomized, placebo‐controlled, parallel group, escalation was conducted six sequential panels – apixaban 2.5, 5, 10 25 mg twice daily once...

To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on major components renal glucose reabsorption (decreased maximum reabsorptive capacity [TmG], increased splay, and reduced threshold), using pancreatic/stepped hyperglycemic clamp (SHC) technique.Subjects with type diabetes (n=12) matched healthy subjects underwent pancreatic/SHC (plasma range 5.5-30.5 mmol/L) at baseline after 7 days dapagliflozin treatment. A pharmacodynamic model was developed to...

Apixaban is an oral, direct, factor-Xa inhibitor approved for thromboprophylaxis in patients who have undergone elective hip or knee replacement surgery and prevention of stroke systemic embolism with non-valvular atrial fibrillation. This open label, parallel group study investigated effects extremes body weight on apixaban pharmacokinetics, pharmacodynamics, safety tolerability.

Abstract This open‐label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment healthy following a single 10‐mg oral dose. The primary analysis determined the relationship between AUC ∞ 24‐hour creatinine clearance (CL cr ) as measure of function. relationships CL iohexol clearance, estimated (Cockcroft‐Gault equation), glomerular filtration rate (modification diet disease [MDRD] equation) were also assessed....

Aim Apixaban is an orally active inhibitor of coagulation factor Xa and eliminated by multiple pathways, including renal non‐renal elimination. Non‐renal elimination pathways consist metabolism cytochrome P450 ( CYP ) enzymes, primarily CYP3A4 , as well direct intestinal excretion. Two single sequence studies evaluated the effect ketoconazole (a strong dual P ‐glycoprotein [ ‐gp]) diltiazem moderate a ‐gp inhibitor) on apixaban pharmacokinetics in healthy subjects. Method In study, 18...

This study assessed the effect of differences in renal function on pharmacokinetics and pharmacodynamics dapagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor for treatment type 2 diabetes mellitus (T2DM).A single 50 mg dose dapagliflozin was used to assess five groups: healthy non-diabetic subjects; patients with T2DM normal kidney mild, moderate or severe impairment based estimated creatinine clearance. Subsequently, 20 once daily multiple doses were evaluated T2DM. Formation...

Currently, there are no direct comparisons of apixaban and rivaroxaban, two new oral factor Xa inhibitors approved for management thromboembolic disorders.Compare the pharmacokinetics anti-factor activity (AXA) rivaroxaban.In this randomized, open-label, two-period, two-treatment crossover study, healthy subjects (N=14) received 2.5 mg twice daily (BID) rivaroxaban 10 once (QD) 4 days with a ≥4.5-day washout. Plasma samples were obtained pharmacokinetic AXA assessments; parameters calculated...

Dapagliflozin, a selective, orally active inhibitor of the renal sodium-glucose co-transporter type 2 (SGLT2) is in development for treatment diabetes mellitus (T2DM). Here, pharmacokinetics (PK) and pharmacodynamics (PD) dapagliflozin were evaluated healthy Japanese subjects with T2DM.Two studies conducted: single-ascending dose (SAD) study (2.5-50 mg) 32 multiple-ascending (MAD) (2.5-20 mg QD 14 days) 36 T2DM. Safety tolerability assessed both studies. Single multiple PK its inactive major...

A double-blind crossover study was conducted in four CYP2C19 genotype–defined metabolizer groups to assess whether increase clopidogrel dosing can overcome reduced pharmacodynamic response poor metabolizers (PMs). Ten healthy subjects each of were randomized a regimen 300-mg loading dose (LD) and 75-mg/day maintenance (MD) for 4 days followed by 600-mg LD 150 mg/day MD, or vice versa. The exposure levels clopidogrel's active metabolite H4 (clopi-H4) PMs 71% lower on the 64% 150-mg/day than...

The effects of age and sex on apixaban pharmacokinetics pharmacodynamics were studied. This was an open-label, single-dose, 2 × factorial study. Healthy young (aged 18–40 years) elderly ≥65 male female subjects received a single oral 20 mg dose apixaban. Blood urine samples collected for pharmacokinetic pharmacodynamic (blood only) analyses. Subjects monitored adverse events throughout the Seventy-nine enrolled into four groups: males (n = 20), females 20) 19). Age did not affect maximum...

This study aimed to assess changes in the plasma concentrationss of 4β-hydroxycholesterol (4βHC) against intravenous (i.v.) and oral midazolam (MDZ) pharmacokinetics (PK) after administration a potent CYP3A inhibitor [ketoconazole (KETO)] inducer [rifampicin (RIF)].Thirty-two healthy subjects (HS) were allocated into three groups 12 each KETO RIF 10 placebo group (PLB). All HS randomized receive i.v. MDZ on day 1 or 2 15 16 receiving (600 mg once daily), (400 daily) PLB for weeks. Subjects...

To determine the absolute oral bioavailability (F(p.o.) ) of saxagliptin and dapagliflozin using simultaneous intravenous ¹⁴C-microdose/therapeutic dosing (i.v.micro + oraltherap).The F(p.o.) values were determined in healthy subjects (n = 7 8, respectively) following concomitant administration single i.v. micro doses with unlabelled oraltherap doses. Accelerator mass spectrometry liquid chromatography-tandem used to quantify labelled drug, respectively.The geometric mean point estimates...

This analysis describes the population pharmacokinetics ( PPK ) of apixaban in nonvalvular atrial fibrillation NVAF subjects, and quantifies impact intrinsic extrinsic factors on exposure. The model was developed using data from phase I–III studies. Apixaban exposure characterized by a two‐compartment with first‐order absorption elimination. Predictive covariates apparent clearance included age, sex, Asian race, renal function, concomitant strong/moderate cytochrome P450 CYP...

Journal Article Depletion of Glutathione in Normal and Malignant Human Cells In Vivo by Buthionine Sulfoximine: Clinical Biochemical Results Get access P. J. O'Dwyer, O'Dwyer * Fox Chase Cancer CenterPhiladelphia, Pa. *Correspondence to : M.D., Department Medical Oncology, Center, 7701 Burholme AVE., Philadelphia, PA 19111. Search for other works this author on: Oxford Academic PubMed Google Scholar T. C. Hamilton, Hamilton R. Young, Young F. LaCreta, LaCreta N. Carp, Carp K. D. Tew, Tew...

Dapagliflozin increases urinary glucose excretion by selectively inhibiting renal sodium-glucose transporter 2, an insulin-independent mechanism of action that may be complementary to other oral antidiabetes drugs. The current studies assessed the potential for pharmacokinetic (PK) interaction between dapagliflozin and pioglitazone, metformin, glimepiride or sitagliptin in healthy subjects following single-dose administration.In open-label, randomized, three-period, three-treatment crossover...

Aim To assess pharmacokinetic and pharmacodynamic interactions between naproxen (a non‐steroidal anti‐inflammatory drug) apixaban (an oral, selective, direct factor‐ X a inhibitor). Method In this randomized, three period, two sequence study, 21 healthy subjects received single oral dose of 10 mg, 500 mg or co‐administration both. Blood samples were collected for determination pharmacokinetics pharmacodynamics (anti‐ activity, international normalized ratio [ INR ] arachidonic acid–induced...

Aims Dapagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that decreases serum by reducing renal reabsorption, thereby promoting urinary excretion. primarily metabolized via the uridine diphosphate‐glucuronosyltransferase (UGT)1A9 pathway to its major inactive metabolite, dapagliflozin 3‐O‐glucuronide. The aim of this study was evaluate potential for drug‐drug interaction between and two UGT1A9 modulators. Methods results open‐label, non‐randomized, single‐sequence...