Evaluation of a pharmacokinetic interaction between valsartan and simvastatin in healthy subjects

ABSTRACT

Objective: The potential for a pharmacokinetic drug interaction between valsartan, an antihypertensive drug, and simvastatin, a lipid-lowering agent, was investigated in this study. This was an open-label, multiple-dose, randomized, three-period, cross over study in 18 healthy subjects. Each subject received one 160?mg valsartan tablet or one 40?mg simvastatin tablet or co-administration of valsartan (160?mg) and simvastatin (40?mg) tablets for 7 days, with a 7?day inter-dose washout period. The steady-state pharmacokinetics of valsartan, simvastatin β?hydroxy acid (active metabolite of simvastatin) and simvastatin (pro-drug) were determined on day 7 of each dosing period.

Results: The results were interpreted based on the point estimates and the 90% confidence intervals.italic> These results indicated that the area under the curve of plasma concentration from 0 to 24 hours (AUC_(0–24)) of valsartan, simvastatin β?hydroxy acid and simvastatin was increased by 14%, 19%, and 23%, respectively, with the combination treatment. In addition, the maximum concentration (C_max) of valsartan and simvastatin β?hydroxy acid was increased by 10% and 22%, respectively, and the C_max of simvastatin was decreased by 26% with the combination treatment. All treatments were safe and well tolerated.

Conclusions: Based on the wide therapeutic dosage ranges of valsartan and simvastatin, and the highly variable pharmacokinetics of three analytes, the observed differences in the exposure and C_max of valsartan, simvastatin β?hydroxy acid and simvastatin in the combination treatment are unlikely to be of clinical relevance.     

Evaluation of the potential for steady-state pharmacokinetic and pharmacodynamic interactions between the DPP-4 inhibitor linagliptin and metformin in healthy subjects

ABSTRACT

Objective: Linagliptin (BI 1356) is a novel, orally available inhibitor of dipeptidyl peptidase-4 (DPP-4). Linagliptin improves glycaemic control in type 2 diabetic patients by increasing the half-life of the incretin hormone glucagon-like peptide-1 (GLP-1). Linagliptin is expected to be used as monotherapy or in combination with other antihyperglycaemic agents. This study was conducted to investigate potential pharmacokinetic or pharmacodynamic interactions between linagliptin and metformin.

Methods: This randomised, monocentric, open-label, two-way crossover design study was conducted in 16 healthy male subjects. Linagliptin (10?mg/day)?and metformin (850?mg three times daily) were each administered alone and concomitantly. The steady-state pharmacokinetics of linagliptin and metformin and the inhibition of DPP-4 activity were determined at the end of each dosing period.

Results: Co-administration of linagliptin had no apparent effect on metformin exposure (metformin AUC_τ,ss; geometric mean ratio [GMR] co-administration:individual administration was 1.01; 90% confidence interval [CI] was 0.89–1.14). Effects on maximum concentration (C_max,ss) were small (GMR: 0.89; 90% CI: 0.78–1.00). Co-administration of metformin did not significantly affect C_max,ss of linagliptin (GMR: 1.03; 90% CI: 0.86–1.24), but increased AUC_τ,ss by 20% (GMR: 1.20; 90% CI: 1.07–1.34). Metformin alone had no effect on DPP-4 activity, and the inhibition of DPP-4 caused by linagliptin was not affected by concomitant administration of metformin. Tolerability was good whether linagliptin and metformin were administered alone or concomitantly. No serious adverse events occurred and the frequency of adverse events was low; 7 events in 6 subjects. The most frequent events were related to the gastrointestinal tract, as expected with metformin. Importantly, no subjects experienced signs or symptoms relating to episodes of hypoglycaemia.

Conclusion: In this small, multiple dose study carried out in healthy subjects, co-administration of linagliptin with metformin did not have a clinically relevant effect on the pharmacokinetics or pharmacodynamics of either agent. This study suggests linagliptin and metformin can safely be administered concomitantly in type 2 diabetes patients without dose adjustment; larger, longer-term clinical trials in diabetic patients are underway.     

Study of the pharmacokinetic interaction of vildagliptin and metformin in patients with type 2 diabetes*

ABSTRACT

Objective: Metformin is widely used for treating patients with type 2 diabetes, often as first-line therapy; however, many patients with type 2 diabetes are unable to maintain adequate glycemic control with metformin alone. Vildagliptin, an orally active, potent and selective dipeptidyl peptidase IV (DPP-4) inhibitor, may represent an appropriate antihyperglycemic agent for combination with metformin to improve glycemic control in such patients. This study assessed the effects of coadministration of vildagliptin and metformin on the steady-state pharmacokinetics of each drug.

Research design and methods: In this open-label, single-center, randomized, three-period, three-treatment crossover study, 17 patients with type 2 diabetes received vildagliptin 100?mg once daily; metformin 1000?mg once daily; or vildagliptin 100?mg once daily plus metformin 1000?mg once daily. Blood samples for pharmacokinetic sampling were taken frequently on the final day (Day 5) of each treatment period. Lack of pharmacokinetic interaction was defined as the ratio of geometric mean (GMR) and 90% confidence interval (CI) for combination:monotherapy being within the range 0.80–1.25.

Results: Coadministration with metformin had no effect on vildagliptin AUC_0–24 (GMR, 0.94; 90% CI 0.90, 0.99) although there was an 18% decrease in vildagliptin C_max (GMR 0.82; 90% CI 0.73, 0.91). Coadministration with vildagliptin had no effect on metformin C_max (GMR 1.04; 90% CI 0.94, 1.16). but caused a 15% increase in AUC_0–24 (GMR 1.15; 90% CI 1.06, 1.25). Both monotherapies and combination therapy were well tolerated. Seven patients reported a total of 10 adverse events; none was serious.

Conclusions: Coadministration of vildagliptin and metformin had a small effect on the pharmacokinetics of each drug in patients with type 2 diabetes; however, this is not likely to be clinically relevant. This small, open-label trial suggests that vildagliptin could be coadministered with metformin without any dose adjustment for either agent.     

Effect of the novel oral dipeptidyl peptidase IV inhibitor vildagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects*

ABSTRACT

Objective: Vildagliptin is a potent and selective dipeptidyl peptidase?IV (DPP?4) inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha and beta-cell responsiveness to glucose. This study assessed the effect of multiple doses of vildagliptin 100?mg once daily on warfarin pharmacokinetics and pharmacodynamics following a single 25?mg oral dose of warfarin sodium.

Research design and methods: Open-label, randomized, two-period, two-treatment crossover study in 16 healthy subjects.

Results: The geometric mean ratios (co-administration vs. administration alone) and 90% confidence intervals (CIs) for the area under the plasma concentration-time curve (AUC) of vildagliptin, R- and S?warfarin were 1.04 (0.98, 1.11), 1.00 (0.95, 1.04) and 0.97 (0.93, 1.01), respectively. The 90% CI of the ratios for vildagliptin, R- and S?warfarin maximum plasma concentration (C_max) were also within the equivalence range 0.80–1.25. Geometric mean ratios (co-administration vs. warfarin alone) of the maximum value and AUC for prothrombin time (PT_max, 1.00 [90% CI 0.97, 1.04]; AUC_PT, 0.99 [0.97, 1.01]) and international normalized ratios (INR_max, 1.01 [0.98, 1.05]; AUC_INR, 0.99 [0.97, 1.01]) were near unity with the 90% CI within the range 0.80–1.25. Vildagliptin was well tolerated alone or co-administered with warfarin; only one adverse event (upper respiratory tract infection in a subject receiving warfarin alone) was reported, which was judged not to be related to study medication.

Conclusions: Co-administration of warfarin with vilda­gliptin did not alter the pharmacokinetics and pharmaco­dynamics of R- or S?warfarin. The pharmacokinetics of vildagliptin were not affected by warfarin. No dosage adjustment of either warfarin or vildagliptin is necessary when these drugs are co-medicated.     

Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects

AIMS: The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites. METHODS: In an open, randomized (for midazolam treatment sequence) study, 18 healthy male subjects received single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart) alone, repeated doses of roflumilast (500 microg once daily for 14 days) alone, and repeated doses of roflumilast together with single doses of midazolam (2 mg oral and 1 mg i.v., 1 day apart). RESULTS: A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam. Point estimates (90% CI) were 0.97 (0.84, 1.13) for the AUC of i.v. midazolam and 0.98 (0.82, 1.17) for that of oral midazolam with and without roflumilast. CONCLUSIONS: Therapeutic steady state concentrations of roflumilast and its N-oxide do not alter the disposition of the CYP3A substrate midazolam in healthy subjects. This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4.     

Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects

AIMS: To evaluate potential pharmacokinetic interactions between phenobarbitone and retigabine, a new antiepileptic drug. METHODS: Fifteen healthy men received 200 mg of retigabine on day 1. On days 4-32, phenobarbitone 90 mg was administered at 22.00 h. On days 26-32, increasing doses of retigabine were given to achieve a final dose of 200 mg every 8 h on day 32. The pharmacokinetics of retigabine were determined on days 1 and 32, and those for phenobarbitone on days 25 and 31. RESULTS: After administration of a single 200 mg dose, retigabine was rapidly absorbed and eliminated with a mean terminal half-life of 6.7 h, a mean AUC of 3936 ng x ml(-1) x h and a mean apparent clearance of 0.76 l x h(-1) x kg(-1). Similar exposure to the partially active acetylated metabolite (AWD21-360) of retigabine was observed. After administration of phenobarbitone dosed to steady-state, the pharmacokinetics of retigabine at steady-state were similar (AUC of 4433 ng x ml(-1) x h and t1/2 of 8.5 h) to those of retigabine alone. The AUC of phenobarbitone was 298 mg x l(-1) x h when administered alone and 311 mg x ml(-1) x h after retigabine administration. The geometric mean ratios and 90% confidence intervals of the AUC were 1.11 (0.97, 1.28) for retigabine, 1.01 (0.88, 1.06) for AWD21-360 and 1.04 (0.96, 1.11) for phenobarbitone. Individual and combined treatments were generally well tolerated. One subject was withdrawn from the study on day 10 due to severe abdominal pain. Headache was the most commonly reported adverse event. No clinically relevant changes were observed in the electrocardiograms, vital signs or laboratory measurements. CONCLUSIONS: There was no pharmacokinetic interaction between retigabine and phenobarbitone in healthy subjects. No dosage adjustment is likely to be necessary when retigabine and phenobarbitone are coadministered to patients.     

Pharmacokinetic interaction between ezetimibe and lovastatin in healthy volunteers*

SUMMARY

Background: Ezetimibe (Zetia?) is a novel inhibitor of intestinal absorption of cholesterol that is approved for the treatment of primary hypercholesterolemia. In a separate pilot study, co-administration of ezetimibe and lovastatin resulted in a significant pharmacodynamic interaction, leading to an additive reduction in LDL-C. The current study was designed to further investigate the potential for pharmacokinetic interaction between ezetimibe and lovastatin.

Methods: This was a randomized, open-label, 3-way crossover study in 18 healthy adult volunteers. All subjects received the following treatments orally once daily for 7 days: ezetimibe 10?mg, lovastatin 20?mg, or ezetimibe 10?mg plus lovastatin 20?mg. Plasma samples obtained on day 7 were evaluated for steady-state pharmacokinetics of ezetimibe (unconjugated), total ezetimibe (ezetimibe and ezetimibe-glucuronide conjugate), lovastatin, and β-hydroxylovastatin.

Results: Co-administration of ezetimibe with lovastatin did not affect the pharmacokinetics of ezetimibe. There were no significant differences in the exposure to total ezetimibe, ezetimibe-glucuronide and ezetimibe after co-administration with lovastatin vs. ezetimibe given alone. Co-administration of ezetimibe with lovastatin had no significant effect on the exposure to either lovastatin or β-hydroxylovastatin. The point estimates based on the log-transformed C_max and AUC values for lovastatin and β-hydroxylovastatin were 113% and 119%, respectively, for co-administration of ezetimibe with lovastatin vs. lovastatin administration alone. Co-administration therapy with ezetimibe and lovastatin was safe and well tolerated.

Conclusions: Ezetimibe did not significantly affect the pharmacokinetics of lovastatin or β-hydroxylovastatin and vice versa. Co-administration of ezetimibe and lovastatin is unlikely to cause a clinically significant pharmacokinetic drug interaction.     

A study of the pharmacokinetic interactions of the direct renin inhibitor aliskiren with metformin,pioglitazone and fenofibrate in healthy subjects*

ABSTRACT

Objective: Hypertension and type 2 diabetes are common comorbidities, thus many patients receiving antihypertensive medication require concomitant therapy with hypoglycemic or lipid-lowering drugs. The aim of these three studies was to investigate the pharmacokinetics, safety and tolerability of aliskiren, a direct renin inhibitor for the treatment of hypertension, co-administered with the glucose-lowering agents metformin or pioglitazone or the lipid-lowering agent fenofibrate in healthy volunteers.

Methods: In three open-label, multiple-dose studies, healthy volunteers (ages 18 to 45 years) received once-daily treatment with either metformin 1000?mg (n?=?22), pioglitazone 45?mg (n?=?30) or fenofibrate 200?mg (n?=?21) and aliskiren 300?mg, administered alone or co-administered in a two-period study design. Blood samples were taken frequently on the last day of each treatment period to determine plasma drug concentrations.

Results: Co-administration of aliskiren with metformin decreased aliskiren area under the plasma concentration–time curve during the dose interval (AUC_τ) by 27% (geometric mean ratio [GMR] 0.73; 90% confidence interval [CI] 0.64, 0.84) and maximum observed plasma concentration (C_max) by 29% (GMR 0.71; 90% CI 0.56, 0.89) but these changes were not considered clinically relevant. Co-administration of aliskiren with fenofibrate had no effect on aliskiren AUC_τ (GMR 1.05; 90% CI 0.96, 1.16) or C_max (GMR 1.05; 90% CI 0.80, 1.38); similarly, co-administration of aliskiren with pioglitazone had no effect on aliskiren AUC_τ (GMR 1.05; 90% CI 0.98, 1.13) or C_max (GMR 1.01; 90% CI 0.84, 1.20). All other AUC_τ and C_max GMRs for aliskiren, metformin, pioglitazone, ketopioglitazone, hydroxypioglitazone and fenofibrate were close to unity and the 90% CI were contained within the bioequivalence range of 0.80 to 1.25.

Conclusion: Co-administration of aliskiren with metformin, pioglitazone or fenofibrate had no significant effect on the pharmacokinetics of these drugs in healthy volunteers. These findings indicate that aliskiren can be co-administered with metformin, pioglitazone or fenofibrate without the need for dose adjustment.     

Evaluation of a pharmacokinetic interaction between remacemide hydrochloride and phenobarbitone in healthy males

AIMS: To determine whether there is a pharmacokinetic interaction between the antiepileptic drugs remacemide and phenobarbitone. METHODS: In a group of 12 healthy adult male volunteers, the single dose and steady-state kinetics of remacemide were each determined twice, once in the absence and once in the presence of phenobarbitone. The effect of 7 days remacemide intake on initial steady-state plasma phenobarbitone concentrations was also investigated. RESULTS: Apparent remacemide clearance (CL/F) and elimination half-life values were unchanged after 7 days intake of the drug in the absence of phenobarbitone (1.25 +/- 0.32 vs 1.18 +/- 0.22 l kg(-1) h(-1) and 3.29 +/- 0.68 vs 3.62 +/- 0.85 h, respectively). Concomitant administration of remacemide with phenobarbitone resulted in an increase in the estimated CL/F of remacemide (1.25 +/- 0.32 vs 2.09 +/-0.53 l kg-1 h-1), and a decreased remacemide half-life (3.29 +/- 0.68 vs 2.69 +/- 0.33 h). The elimination of the desglycinyl metabolite of remacemide also appeared to be increased after the phenobarbitone intake (half-life 14.72 +/- 2.82 vs 9.61 +/- 5.51 h, AUC 1532 +/- 258 vs 533 +/- 281 ng ml(-1) h). Mean plasma phenobarbitone concentrations rose after 7 days of continuing remacemide intake (12.67 +/- 1.31 vs 13.86 +/- 1.81 microgram ml(-1)). CONCLUSIONS: Phenobarbitone induced the metabolism of remacemide and that of its desglycinyl metabolite. Remacemide did not induce its own metabolism, but had a modest inhibitory effect on the clearance of phenobarbitone.     

An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug

Fixed-dose combinations development requires pharmacokinetic drug-drug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.     

Evaluation of pharmacokinetic interaction between cetirizine and ritonavir, an HIV-1 protease inhibitor, in healthy male volunteers

Background Serious adverse effects have been observed with some non-sedative H₁-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this study was to evaluate the potential of pharmacokinetic interaction between cetirizine and ritonavir, the most potent cytochrome P ₄₅₀ (CYP) inhibitor.Methods An open-label, single-center, one-sequence crossover pharmacokinetic study was conducted in three running periods: cetirizine (CTZ) alone, ritonavir (RTV) alone and then CTZ plus RTV. For each period, steady-state pharmacokinetics were obtained. RTV and CTZ plasma concentrations were determined using validated liquid chromatography methods. The statistical method was based on a 90% confidence interval (CI) for the ratio of population geometric means (combination/drug alone) for each drug and for each parameter [area under the plasma concentration versus time curve (AUC_0-,ss), value of maximum plasma concentration (C_max,ss)] and compared to bioequivalence ranges 80–125% and 70–143% for AUC_0-,ss and C_max,ss, respectively.Results Among the 17 male subjects enrolled (26.4±8.6 years), 16 completed the study (1 withdrawal after the first period). The RTV pharmacokinetic parameter values were not affected by CTZ co-treatment. With RTV, a 42% increase in the CTZ AUC_0-,ss (3406 versus 4840 gh/l, 90% CI of 128–158%), a 53% increase in the CTZ elimination half-life (7.8 h versus 11.9 h, P = 0.001), a slight increase (15%) in the CTZ apparent volume of distribution (V_d,ss/ f) (34.7 l versus 39.8 l, P = 0.035), a 29% decrease in the CTZ apparent total body clearance (49.9 ml/min versus 35.3 ml/min, P<0.001) and bioequivalent C_max,ss (374 g/l versus 408 g/l) were observed. No serious drug related adverse effects were notified.Conclusions CTZ does not significantly affect the pharmacokinetic parameters of RTV, and the association does not, thus, require a modification of the dosage of the protease inhibitor. The increased extent of exposure to CTZ in healthy subjects, in the presence of RTV administered at high doses, remained in the same range as previously observed in the elderly or in mildly renally impaired subjects.Presented in part at the 42nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, California, 27–30 September 2002, Poster H-1718.     

Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers

Vildagliptin is a novel antidiabetic agent that is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV, the enzyme responsible for degradation of the incretin hormones. This open-label, randomized, 3-period crossover study investigated the potential for pharmacokinetic interactions in 18 healthy subjects during coadministration of vildagliptin and digoxin. Subjects were randomized to receive each of 3 treatments: vildagliptin 100 mg qd, digoxin (0.5 mg, then 0.25 mg qd on days 2-7), and the combination vildagliptin/digoxin for 7 days. Coadministration of digoxin with vildagliptin had no effect on exposure to vildagliptin (geometric mean ratios [90% confidence interval]: AUC(0-24h), 0.99 [0.95-1.03]; C(max), 0.95 [0.85-1.06]) or to digoxin (AUC(0-24h), 1.02 [0.94-1.12]; C(max), 1.08 [0.97-1.20]). In addition, no changes in t(max), t((1/2)), and CL/F were observed for either drug. These results indicate that no dose adjustment is necessary when vildagliptin and digoxin are coadministered.     

Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and Ginkgo biloba extracts in healthy subjects

Abstract

1. Ginkgo biloba extract (GBE) is one of the most commonly used herbal remedies worldwide. It is usually concomitantly administrated with statins to treat diseases in geriatric patients. We aim to determine the influence of GBE on the pharmacokinetics (PK) and pharmacodynamics of simvastatin, which is currently unknown.

2. An open-label, randomized, two-period, two-treatment, balanced, crossover study was performed in 14 healthy volunteers. Subjects received simvastatin 40?mg once daily, co-treated with placebo or GBE 120?mg twice daily. Each treatment was administered for 14?d, separated by a wash-out period of 1 month. Simvastatin, simvastatin acid and lipoprotein concentrations were assessed.

3. GBE administration reduced mean simvastatin area under the curve (AUC)_0–24, AUC_0–∞ and C_max by 39% (p?=?0.000), 36%(p?=?0.001) and 32% (p?=?0.002), respectively, but did not cause significant differences in simvastatin acid PK or its cholesterol-lowering efficacy.

4. GBE consumption decreased simvastatin system exposure, but did not affect simvastatin acid PK. However, we cannot rule out the possibility for a pharmacodynamic interaction between GBE and simvastatin in vivo.     

Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers

This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine. Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan Cmax was significantly higher following combination treatment with fluoxetine (52.5 +/- 11.9 ng/ml vs. 44.3 +/- 10.9 ng/ml, p = 0.023). Mean AUC0-infinity was not significantly affected by fluoxetine coadministration (353 +/- 55.7 ng.h/ml vs. 333 +/- 33.6 ng.h/ml, p = 0.059). Confidence interval analysis (90%) of log-transformed pharmacokinetic parameters showed that the confidence interval for AUC0-infinity was within the 80% to 125% limit for equivalence, but Cmax was not (90% CI 106%-134% of the reference mean). Adverse events were mild to moderate in intensity, and no clinically significant treatment effects on vital signs or ECGs were observed. The results show that fluoxetine has only a modest effect on almotriptan Cmax. Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted.     

Assessment of the pharmacokinetics of co-administered metformin and lobeglitazone,a thiazolidinedione antihyperglycemic agent,in healthy subjects

Abstract

Objective:

Lobeglitazone as a thiazolidinedione antihyperglycemic agent activates peroxisome proliferator-activated receptor (PPAR) γ and may be suitable as monotherapy or in combination with other antihyperglycemic agents. The primary objective of this study was to investigate potential pharmacokinetic interactions between lobeglitazone and metformin in healthy Korean subjects.     

Thorough QT study of the effects of vildagliptin,a dipeptidyl peptidase IV inhibitor,on cardiac repolarization and conduction in healthy volunteers

Abstract

Objective:

This randomized, double-blind study evaluated the effects of vildagliptin, a dipeptidyl peptidase IV inhibitor for treating type 2 diabetes, on cardiac repolarization and conduction.