Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Drug Investig ; 33(5): 333-42, 2013 May.
Article in English | MEDLINE | ID: mdl-23519576

ABSTRACT

BACKGROUND: Dabigatran etexilate is a pro-drug of the oral reversible direct thrombin inhibitor dabigatran that interacts with the active site in the catalytic domain of the thrombin molecule. OBJECTIVE: To assess the electrophysiological effects of therapeutic and supratherapeutic doses of dabigatran etexilate in healthy subjects, a thorough QT study was performed. METHODS: In this single-centre, blinded, placebo- and active-controlled, four-period, crossover study, 40 healthy Caucasian subjects (20 women and 20 men) received single oral doses of dabigatran etexilate (150 mg and 600 mg), moxifloxacin 400 mg (positive control) or placebo, in a randomized order. Electrocardiogram (ECG) profiles were recorded at baseline and during the randomized study treatment in each period. The individually heart-rate-corrected QT interval (QTcI) was the primary parameter. The primary endpoint was the mean of these QTcI values obtained at 1.5, 2 and 3 h following study drug administration minus the mean of the time-matched QTcI values obtained at baseline day -1. The hypothesis tested was that the difference between each of the two doses of dabigatran etexilate (150 mg and 600 mg) and placebo, for the mean time-matched change from baseline (CfB) of QTcI between 1.5 and 3 h (the primary endpoint), was greater than or equal to 10 ms. Secondary endpoints were the time-matched CfB of QTcI between 0.5 and 24 h post-dose. RESULTS: All subjects completed the study without premature discontinuation and all treatments were well tolerated. Following dabigatran etexilate administration, the mean values of the placebo-adjusted time-matched CfB of QTcI between 1.5 and 3 h post-dose were close to 0; the upper bound of the two-sided 90 % confidence interval (CI) was 1.4 ms for dabigatran etexilate 150 mg and 1.3 ms for dabigatran etexilate 600 mg. The placebo-adjusted time-matched CfB of QTcI remained close to 0 at all time points, and all 90 % CIs were between -5 ms and 5 ms, well below the pre-defined non-inferiority margin of 10 ms. CONCLUSION: This thorough QT study demonstrated that therapeutic and fourfold supratherapeutic doses of dabigatran etexilate do not prolong QT intervals.


Subject(s)
Antithrombins/adverse effects , Benzimidazoles/adverse effects , Heart Rate/drug effects , Long QT Syndrome/chemically induced , Pyridines/adverse effects , Administration, Oral , Adult , Analysis of Variance , Antithrombins/administration & dosage , Antithrombins/pharmacokinetics , Benzimidazoles/administration & dosage , Benzimidazoles/pharmacokinetics , Cross-Over Studies , Dabigatran , Electrocardiography , Female , Germany , Humans , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Male , Middle Aged , Pyridines/administration & dosage , Pyridines/pharmacokinetics , Risk Assessment , Risk Factors , Time Factors
2.
J Clin Pharmacol ; 52(2): 243-50, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21868715

ABSTRACT

This study evaluated the potential impact of concomitant digoxin on the pharmacokinetics and pharmacodynamics of dabigatran etexilate, a novel oral direct thrombin inhibitor. Healthy volunteers (n = 23) received 150 mg dabigatran etexilate twice daily on days 1 to 3 and once on day 4 in 1 period. Digoxin was given in another period as a loading dose of 0.5 mg early on day 1 and 0.25 mg in the evening of day 1 and on the mornings of days 2 to 4. In a third treatment period, dabigatran etexilate together with digoxin was given on days 1 to 4. Exposure to dabigatran was not significantly altered with concomitant digoxin-the maximum concentration (Cmax,ss ) and area under the concentration-time curve at steady state over 1 dosing interval (AUCτ,ss ) of dabigatran with and without digoxin were essentially unchanged. The pharmacokinetic profile of digoxin also remained unchanged in the presence of dabigatran etexilate. Dabigatran's anticoagulant effect, assessed by blood coagulation time assays, was not influenced by digoxin. Dabigatran etexilate and digoxin can be coadministered without the need for dose adjustment of either drug.


Subject(s)
Anti-Arrhythmia Agents/administration & dosage , Antithrombins/administration & dosage , Benzimidazoles/administration & dosage , Digoxin/administration & dosage , Pyridines/administration & dosage , Adult , Anti-Arrhythmia Agents/blood , Anti-Arrhythmia Agents/pharmacokinetics , Antithrombins/blood , Antithrombins/pharmacokinetics , Antithrombins/pharmacology , Area Under Curve , Benzimidazoles/blood , Benzimidazoles/pharmacokinetics , Benzimidazoles/pharmacology , Biological Availability , Blood Coagulation/drug effects , Cross-Over Studies , Dabigatran , Digoxin/blood , Digoxin/pharmacokinetics , Drug Interactions , Female , Healthy Volunteers , Humans , Male , Middle Aged , Pyridines/blood , Pyridines/pharmacokinetics , Pyridines/pharmacology
3.
Xenobiotica ; 41(4): 297-311, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21204634

ABSTRACT

The pharmacokinetics and metabolism of BIBF 1120, an oral triple angiokinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), were studied in healthy male volunteers (n = 8) who had received a single oral dose of 100 mg [(14)C]-radiolabelled BIBF 1120 administered as solution. BIBF 1120 was well-tolerated and rapidly absorbed; median time to reach maximum plasma concentrations was 1.3 h and gMean terminal half-life was 13.7 h. A relatively high apparent total body clearance and volume of distribution possibly indicated a high tissue distribution. Plasma concentrations of BIBF 1120 plus carboxylate metabolite BIBF 1202 were lower than the total [(14)C]-radioactivity in plasma, indicating presence of additional metabolites. Total recovery in excreta was 94.7% 1 week post-dose; mass balance was considered complete after 96 h. BIBF 1120 and metabolites were mainly excreted via faeces. The major metabolic pathway for BIBF 1120 was methyl ester cleavage to BIBF 1202. Subsequently, the free carboxyl group of BIBF 1202 was glucuronidated to 1-O-acylglucuronide. Pathways of minor importance were oxidative N-demethylation to yield BIBF 1053, and oxidation of the piperazine moiety and conjugation. Glucuronidation of the parent drug and formylation of the secondary aliphatic amine of the piperazine ring played a minor role.


Subject(s)
Angiogenesis Inhibitors/pharmacokinetics , Indoles/pharmacokinetics , Administration, Oral , Adult , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/metabolism , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacokinetics , Feces/chemistry , Half-Life , Humans , Indoles/administration & dosage , Indoles/metabolism , Male , Middle Aged , Young Adult
4.
Clin Pharmacokinet ; 49(4): 259-68, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20214409

ABSTRACT

Dabigatran etexilate is an oral direct thrombin inhibitor in clinical development for the prevention and treatment of thromboembolic disorders. Following oral administration, dabigatran etexilate is rapidly absorbed and converted into its active form, dabigatran. The aim of this study was to investigate the effect of renal impairment on the pharmacokinetics and pharmacodynamics of dabigatran following administration of a single oral dose of dabigatran etexilate in subjects with renal impairment (150 mg) or end-stage renal disease (ESRD) on maintenance haemodialysis (50 mg). This open-label, parallel-group, single-centre study enrolled 23 subjects with mild, moderate or severe renal impairment (creatinine clearance >50 to < or =80, >30 to < or =50 and < or =30 mL/min, respectively), 6 patients with ESRD and 6 healthy subjects. Blood and urine samples were collected up to 96 hours after dosing for determination of dabigatran pharmacokinetic and pharmacodynamic parameters. Compared with the values in healthy subjects, the area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) values were 1.5-, 3.2- and 6.3-fold higher in subjects with mild, moderate and severe renal impairment. Changes in the maximum plasma concentration (C(max)) were modest, and the time to reach the C(max) was unchanged. In subjects with severe renal impairment, the mean terminal elimination half-life was doubled (28 hours vs 14 hours for control). The AUC for prolongation of pharmacodynamic parameters (the activated partial thromboplastin time and ecarin clotting time) increased in line with the pharmacokinetic changes. In patients with ESRD, the dose-normalized AUC(infinity) was approximately twice the value in the control group. Haemodialysis removed 62-68% of the dose. Dabigatran etexilate was well tolerated in all groups. Exposure to dabigatran is increased by renal impairment and correlates with the severity of renal dysfunction. A decrease in the dose and/or an increase in the administration interval in these patients may be appropriate. In patients with ESRD, dabigatran can be partly removed from the plasma by haemodialysis.


Subject(s)
Anticoagulants/pharmacology , Benzimidazoles/pharmacology , Pyridines/pharmacology , Renal Insufficiency/metabolism , Administration, Oral , Adolescent , Adult , Aged , Anticoagulants/pharmacokinetics , Area Under Curve , Benzimidazoles/pharmacokinetics , Creatinine/pharmacokinetics , Dabigatran , Female , Half-Life , Humans , Male , Metabolic Clearance Rate , Middle Aged , Pyridines/pharmacokinetics , Renal Dialysis , Severity of Illness Index
5.
Am J Cardiovasc Drugs ; 9(1): 59-68, 2009.
Article in English | MEDLINE | ID: mdl-19178132

ABSTRACT

BACKGROUND: Dabigatran etexilate, a novel oral direct thrombin inhibitor, has been approved for prophylaxis of thromboembolism in patients undergoing total knee or total hip replacement, and is under clinical investigation for treatment of venous thromboembolism, prevention of stroke in patients with atrial fibrillation, and the treatment of thromboembolic complications following acute coronary syndromes. OBJECTIVE: To evaluate the potential impact of atorvastatin coadministration on the pharmacokinetics, pharmacodynamics, and safety of dabigatran etexilate. METHODS: Healthy male and female volunteers (n = 22) were recruited to this open, randomized, multiple-dose, three-way crossover study. They received dabigatran etexilate 150 mg twice daily on days 1-3 and once daily on day 4, atorvastatin 80 mg once daily on days 1-4, or both treatments together on days 1-4. RESULTS: Exposure to dabigatran at steady state (area under the drug plasma concentration-time curve at steady state) was reduced by 18% with concomitant atorvastatin administration. An 18% increase in plasma atorvastatin concentration occurred with coadministration of dabigatran etexilate. Exposure to its metabolite 2'-hydroxy-atorvastatin remained essentially unchanged and exposure to 4'-hydroxy-atorvastatin was increased by 15%. The small changes observed are deemed of little clinical relevance given the overall inter-individual variability in the metabolism of atorvastatin. Furthermore, there were no changes in the concentrations of active HMG-CoA reductase inhibitors in plasma following dabigatran etexilate coadministration. Six subjects in the atorvastatin treatment group, six subjects during combination treatment, and eight subjects in the dabigatran treatment group reported adverse events. Most of the adverse events reported were nervous system disorders such as dizziness and headache, and general disorders such as fatigue. All adverse events were resolved at the end of the study. CONCLUSION: Results of this randomized, open-label, three-way crossover design study in healthy male and female volunteers showed that atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of dabigatran, and vice versa, dabigatran etexilate had no impact on the pharmacokinetic/pharmacodynamic profile of atorvastatin. Both drugs were well tolerated when given alone or in combination.


Subject(s)
Anticoagulants/pharmacokinetics , Benzimidazoles/pharmacology , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Pyridines/pharmacology , Pyrroles/pharmacology , Administration, Oral , Adult , Anticoagulants/adverse effects , Anticoagulants/pharmacology , Area Under Curve , Atorvastatin , Benzimidazoles/adverse effects , Benzimidazoles/pharmacokinetics , Cross-Over Studies , Dabigatran , Dose-Response Relationship, Drug , Drug Interactions , Female , Heptanoic Acids/adverse effects , Heptanoic Acids/pharmacokinetics , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Male , Pyridines/adverse effects , Pyridines/pharmacokinetics , Pyrroles/adverse effects , Pyrroles/pharmacokinetics , Sex Factors , Thrombin/antagonists & inhibitors
6.
J Clin Pharmacol ; 48(12): 1411-9, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18827075

ABSTRACT

The impact of moderate hepatic impairment on the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran etexilate was evaluated in an open, parallel-group study. Healthy volunteers (n = 12) and patients with hepatic impairment (Child-Pugh classification B; n = 12) received a single oral dose of 150 mg dabigatran etexilate. The mean values for area under the concentration-time curve, terminal half-life, and renal clearance of dabigatran were comparable between patients with hepatic impairment and healthy volunteers. Conversion of the dabigatran intermediate BIBR1087 to active dabigatran was slower in patients with hepatic impairment, indicating that the liver is partly involved in bioconversion of dabigatran etexilate. However, total drug exposure was comparable between groups; therefore, this observation is of no clinical relevance with respect to the anticoagulant activity of dabigatran. The extent of dabigatran glucuronidation was unchanged by liver disease; glucuronidation capacity was maintained in moderate liver disease. The activated partial thromboplastin time, ecarin clotting time, and thrombin time relationships were essentially identical in both groups. This study shows that moderate hepatic impairment does not affect the PK/PD or safety profile of dabigatran. Therefore, patients with moderate hepatic impairment can be given dabigatran etexilate without the need for dose adjustment.


Subject(s)
Benzimidazoles/pharmacokinetics , Hepatic Insufficiency/metabolism , Pyridines/pharmacokinetics , Thrombin/antagonists & inhibitors , Administration, Oral , Adult , Aged , Anticoagulants/adverse effects , Anticoagulants/pharmacokinetics , Area Under Curve , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Biological Availability , Blood Proteins/metabolism , Dabigatran , Erythema/chemically induced , Female , Glucuronides/biosynthesis , Half-Life , Headache/chemically induced , Hepatic Insufficiency/pathology , Humans , International Normalized Ratio , Male , Middle Aged , Partial Thromboplastin Time , Prodrugs/administration & dosage , Prodrugs/adverse effects , Prodrugs/pharmacokinetics , Prothrombin Time , Pyridines/administration & dosage , Pyridines/adverse effects , Severity of Illness Index , Sex Factors
7.
Clin Pharmacokinet ; 47(1): 47-59, 2008.
Article in English | MEDLINE | ID: mdl-18076218

ABSTRACT

OBJECTIVES: To investigate the pharmacokinetic and pharmacodynamic profile of dabigatran in healthy elderly subjects; to assess the intra- and interindividual variability of dabigatran pharmacokinetics in order to assess possible gender differences; and to assess the effect of pantoprazole coadministration on the bioavailability of dabigatran. STUDY DESIGN AND SETTING: Open-label, parallel-group, single-centre study, consisting of a baseline screening visit, 7-day treatment period and post-study examination visit. SUBJECTS AND INTERVENTION: 36 healthy elderly subjects (aged > or =65 years) with a body mass index of 18.5-29.9 kg/m(2). Subjects were randomized to receive dabigatran etexilate either with or without coadministration of pantoprazole. Dabigatran etexilate was administered as capsules at 150 mg twice daily over 6 days and once on the morning of day 7. Pantoprazole was administered at 40 mg twice daily, starting 2 days prior to dabigatran etexilate administration and ending on the morning of day 7. MAIN OUTCOME MEASURES: The primary pharmacokinetic measurements included the area under the plasma concentration-time curve at steady state (AUC(ss)), maximum (C(max,ss)) and minimum (C(min,ss)) plasma concentrations at steady state, terminal half-life (t((1/2))), time to reach C(max,ss) and renal clearance of dabigatran. The secondary pharmacokinetic parameters included the mean residence time, total oral clearance and volume of distribution. The pharmacodynamic parameters measured were the blood coagulation parameters ecarin clotting time (ECT) and activated partial thromboplastin time (aPTT). RESULTS: With twice-daily administration of dabigatran etexilate, plasma concentrations of dabigatran reached steady state within 2-3 days, which is consistent with a t((1/2)) of 12-14 hours. The mean (SD) peak plasma concentrations on day 4 of treatment in male and female elderly subjects were 256 ng/mL (21.8) and 255 ng/mL (84.0), respectively. The peak plasma concentrations were reached after a median of 3 hours (range 2.0-4.0 hours). Coadministration with pantoprazole decreased the average bioavailability of dabigatran (the AUC(ss)) by 24% (day 4; 90% CI 7.4, 37.8) and 20% (day 7; 90% CI 5.2, 33.3). Intra- and interindividual pharmacokinetic variability in the overall population was low (<30% coefficient of variation), indicating that dabigatran has a predictable pharmacokinetic profile. Prolongation of the ECT and aPTT correlated with, and paralleled, the plasma concentration-time profile of dabigatran, which demonstrates a rapid onset of action without a time delay, and also illustrates the direct mode of action of the drug on thrombin in plasma. The ECT increased in direct proportion to the plasma concentration, and the aPTT displayed a linear relationship with the square root of the plasma concentration. The mean AUC(ss) was 3-19% higher in female subjects than in male subjects, which was likely due to gender differences in creatinine clearance. The safety profile of dabigatran was good, with and without pantoprazole coadministration. CONCLUSIONS: Dabigatran demonstrated reproducible and predictable pharmacokinetic and pharmacodynamic characteristics, together with a good safety profile, when administered to healthy elderly subjects. Minor gender differences were not considered clinically relevant. The effects of pantoprazole coadministration on the bioavailability of dabigatran were considered acceptable, and dose adjustment is not considered necessary.


Subject(s)
2-Pyridinylmethylsulfinylbenzimidazoles/pharmacology , Benzimidazoles/pharmacokinetics , Pyridines/pharmacokinetics , 2-Pyridinylmethylsulfinylbenzimidazoles/administration & dosage , Administration, Oral , Aged , Aged, 80 and over , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/pharmacology , Anticoagulants/administration & dosage , Anticoagulants/blood , Anticoagulants/pharmacokinetics , Area Under Curve , Benzimidazoles/administration & dosage , Benzimidazoles/blood , Biological Availability , Blood Coagulation/drug effects , Capsules , Chromatography, Liquid , Dabigatran , Diarrhea/chemically induced , Female , Flatulence/chemically induced , Hematoma/chemically induced , Humans , Male , Metabolic Clearance Rate/drug effects , Pantoprazole , Partial Thromboplastin Time , Pyridines/administration & dosage , Pyridines/blood , Sex Factors , Tandem Mass Spectrometry , Thrombin/antagonists & inhibitors
8.
Br J Clin Pharmacol ; 64(3): 292-303, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17506785

ABSTRACT

AIMS: The novel direct thrombin inhibitor (DTI), dabigatran etexilate (Boehringer Ingelheim Pharma GmbH & Co. KG), shows potential as an oral antithrombotic agent. Two double-blind, randomized trials were undertaken to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of orally administered dabigatran etexilate in healthy male subjects. METHODS: Dabigatran etexilate or placebo was administered orally at single doses of 10-400 mg (n = 40) or at multiple doses of 50-400 mg three times daily for 6 days (n = 40). Plasma and urine samples were collected over time to determine the PK profile of dabigatran. PD activity was assessed by its effects on blood coagulation parameters: activated partial thromboplastin time (aPTT), prothrombin time (PT), reported as international normalized ratio (INR), thrombin time (TT), and ecarin clotting time (ECT). All adverse events were recorded. RESULTS: Dabigatran etexilate was rapidly absorbed with peak plasma concentrations of dabigatran reached within 2 h of administration. This was followed by a rapid distribution/elimination phase and a terminal phase, with associated estimated half-lives of 8-10 h and 14-17 h with single and multiple dose administrations, respectively. Dabigatran exhibited linear PK characteristics with dose-proportional increases observed in maximum plasma concentration and area under the curve. Steady-state conditions were reached within 3 days with multiple dosing. The mean apparent volume of distribution during the terminal phase (V(z)/F) of 1860 l (range 1430-2400 l) and the apparent total clearance after oral administration (CL(tot)/F) of 2031 ml min(-1) (range 1480-2430), were dose independent. Time curves for aPTT, INR, TT and ECT paralleled plasma concentration-time curves with values increasing rapidly and in a dose-dependent manner. At the highest dose of 400 mg administered three times daily, maximum prolongations over baseline of 3.1 (aPTT), 3.5 (INR), 29 (TT) and 9.5-fold (ECT) were observed. Dabigatran underwent conjugation with glucuronic acid to form pharmacologically active conjugates that accounted for approximately 20% of total dabigatran in plasma. Overall, variability in PK parameters was low to moderate, with an average interindividual coefficient of variation (CV) of approximately 30% and variability in PD parameters was low, with CV < 10%. Of the four assays, TT and ECT exhibited the greatest sensitivity and precision within the anticipated therapeutic dose range. Bleeding events were few and were mild-to-moderate in intensity, occurring only in the higher, multiple dose groups. CONCLUSIONS: These data suggest that dabigatran etexilate is a promising novel oral DTI with predictable PK and PD characteristics and good tolerability. Further investigation of dabigatran etexilate for the treatment and prophylaxis of patients with arterial and venous thromboembolic disorders, acute coronary syndromes and other medical conditions is warranted.


Subject(s)
Anticoagulants/pharmacology , Anticoagulants/pharmacokinetics , Benzimidazoles/pharmacology , Benzimidazoles/pharmacokinetics , Pyridines/pharmacology , Pyridines/pharmacokinetics , Administration, Oral , Adolescent , Adult , Anticoagulants/blood , Area Under Curve , Benzimidazoles/blood , Blood Coagulation Tests , Dabigatran , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Male , Middle Aged , Pyridines/blood
9.
J Clin Pharmacol ; 45(5): 555-63, 2005 May.
Article in English | MEDLINE | ID: mdl-15831779

ABSTRACT

Dabigatran etexilate is an oral low-molecular-weight direct thrombin inhibitor. Following oral administration, dabigatran etexilate is rapidly converted to its active form, dabigatran. The authors investigated the absorption, distribution, and elimination of a single 150-mg dose capsule formulation of dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. In an open-label, 3-way crossover study, dabigatran etexilate was administered to 18 male volunteers in the fasted state, after administration of food and with coadministration of the proton pump inhibitor, pantoprazole. In a subsequent multicenter, open-label study, 59 patients received a single dose of dabigatran etexilate, administered 1 to 3 hours following total hip replacement. In healthy volunteers, food had no effect on the extent of absorption of dabigatran etexilate, although there was reduced interindividual variability for dabigatran maximum plasma concentration and AUC(0-infinity). A decrease in the mean dabigatran AUC(0-infinity) (904 to 705 ng*h/mL) occurred with coadministration of pantoprazole. In patients undergoing total hip replacement, immediate onset of absorption was seen with the maximum plasma concentration of dabigatran occurring after 6 hours. The AUC(0-24) of dabigatran was 88% of the steady-state AUC using a preliminary tablet formulation and 106% of that seen in the healthy volunteer study. Compared with healthy volunteers, the postoperative profile was flattened with delayed peak concentrations. In summary, administration of the dabigatran etexilate capsule with food has no effect on the extent of dabigatran absorption, with a moderate decrease when coadministered with pantoprazole. Adequate plasma concentrations of dabigatran were seen with early postoperative administration of the dabigatran etexilate capsule. These pharmacokinetic characteristics confirm the suitability of this oral solid dosage form for use in future clinical trials.


Subject(s)
Arthroplasty, Replacement, Hip , Benzimidazoles/pharmacokinetics , Omeprazole/analogs & derivatives , Pyridines/pharmacokinetics , Thrombin/antagonists & inhibitors , 2-Pyridinylmethylsulfinylbenzimidazoles , Absorption , Administration, Oral , Adult , Aged , Aged, 80 and over , Area Under Curve , Benzimidazoles/pharmacology , Cross-Over Studies , Dabigatran , Drug Interactions , Female , Food-Drug Interactions , Humans , Male , Metabolic Clearance Rate , Middle Aged , Omeprazole/pharmacology , Pantoprazole , Proton Pump Inhibitors , Sulfoxides/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...