scholarly journals Evaluation of the analgesic activity of single and multiple oral doses of teneligliptin (20 mg/day), using hot air analgesiometer in healthy human volunteers: a randomized, double blind, placebo controlled, cross over study

2020 ◽  
Vol 9 (3) ◽  
pp. 498
Author(s):  
Maleha Butul ◽  
Usharani Pingali ◽  
Chandrasekhar Nutalapati
Keyword(s):  
Single Dose ◽  
Analgesic Activity ◽  
Healthy Subjects ◽  
Pain Threshold ◽  
Pain Tolerance ◽  
Healthy Human ◽  
Hot Air ◽  
Multiple Doses ◽  
Dose Study ◽  
Significant Change

Background DPP-4inhibitors showed analgesic and anti-inflammatory activity in human and animal-studies. DPP-4 inhibitors improved nerve function and thermal nociception in animal models. Aim of the study was to explore analgesic activity of single and multiple doses of teneligliptin 20 mg/day using hot air analgesiometer in healthy human volunteers.Methods: After IEC approval and informed consent, subjects were randomized to receive either teneligliptin 20 mg or placebo in double-blinded manner with standard breakfast. Mean pain threshold and tolerance(sec) using hot air analgesiometer were recorded at baseline and 1 hr, 2 hrs post drug on day1, for single dose study. Subsequently drugs were administered under supervision daily for 6 days and same procedure repeated on day8 for multiple-dose study. After 2 weeks washout, subjects crossed over in period 2 to other formulation and same procedure repeated to determine study parameters. Fasting blood-sugar (FBS) monitored, ADRs recorded in CRF. Statistical analysis done with SPSS20.0.Results: Twelve-healthy subjects (8 males, 4 females) with mean age 33.08±4.69 years, mean BMI 22.6±1.37kg/m2 participated. Single dose teneligliptin produced significant increase in pain threshold (35.9%) and pain tolerance (25.1%) (p<0.0001) at 1hour compared to baseline. With multiple doses, pain threshold increased by 37.1% and pain tolerance by 25.4% (p<0.0001) at 1hour compared to baseline. The increase in pain threshold and tolerance values at 1 and 2 hours were similar. There was no significant change in pain threshold(p=0.4135) and tolerance (p=0.4476) at baseline on day1 and day 8. Placebo showed non-significant change in study parameters. Both treatments well tolerated. FBS of volunteers within normal limits during treatment period and no hypoglycemia reported.Conclusions: Results of our study suggest that teneligliptin20mg in healthy subjects demonstrated significant analgesic activity on day 1 and day 8 compared to baseline & placebo. Its role in painful diabetic conditions can be further explored.

scholarly journals Pharmacokinetics of Tigecycline after Single and Multiple Doses in Healthy Subjects

2005 ◽  
Vol 49 (1) ◽  
pp. 220-229 ◽  
Author(s):  
Gopal Muralidharan ◽  
Marlynne Micalizzi ◽  
John Speth ◽  
Donald Raible ◽  
Steven Troy
Keyword(s):  
Liquid Chromatography ◽  
Single Dose ◽  
Healthy Subjects ◽  
Antimicrobial Agents ◽  
Phase 1 ◽  
Bacterial Species ◽  
Strong Activity ◽  
Single Dose Study ◽  
Multiple Doses ◽  
Dose Study

ABSTRACT Tigecycline, a novel glycylcycline antibiotic, exhibits strong activity against gram-positive, gram-negative, aerobic, anaerobic, and atypical bacterial species, including many resistant pathogens, i.e., vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The safety and tolerability of tigecycline administered as single or multiple doses or at various infusion rates were explored in three phase 1, randomized, double-blind, placebo-controlled studies in healthy subjects. Full pharmacokinetic profiles of tigecycline were determined in two of these studies. Subjects in the single-dose study received 12.5 to 300 mg of tigecycline, which differed with respect to the duration of infusion, subjects' feeding status, and ondansetron pretreatment. Subjects in the ascending multiple-dose study received 25 to 100-mg doses of tigecycline as a 1-h infusion every 12 h. The variable volume and infusion rate study consisted of administration of 100-mg loading dose of tigecycline, followed by 50 mg every 12 h for 5 days. Serum samples were analyzed for tigecycline by validated high-pressure liquid chromatography or liquid chromatography/tandem mass spectrometry methods. Systemic clearance ranged from 0.2 to 0.3 liters/h/kg, and the tigecycline half-life ranged from 37 to 67 h. Tigecycline had a large volume of distribution (7 to 10 liters/kg), indicating extensive distribution into the tissues. Food increased the maximum tolerated single-dose from 100 to 200 mg, but the duration of infusion did not affect tolerability. Side effects, mainly nausea and vomiting, which are common to the tetracycline class of antimicrobial agents, were seen in these studies. Tigecycline exhibits linear pharmacokinetics and is safe and well tolerated in the dose ranges examined.

scholarly journals Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects

Drug Research ◽  
2020 ◽  
Vol 70 (10) ◽  
pp. 472-477
Author(s):  
Thomas Körnicke ◽  
Deepa Arora ◽  
Abdus Samad ◽  
Sigal Kaplan ◽  
Mónika Domahidy ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Renal Elimination ◽  
Modified Release ◽  
Open Label ◽  
Healthy Human ◽  
Dose Study ◽  
Proportional Increase ◽  
Single Ascending Dose Study ◽  
Dose Proportional

Abstract Aim This study assessed the linearity of pharmacokinetics (PK) of trimetazidine (TMZ) modified-release tablets (indicated in adults as an add-on therapy for stable angina pectoris) and measured its renal elimination, safety, and tolerability in healthy subjects. Methods This was a randomized, open-label, single-ascending dose study in healthy subjects. Subjects were administered with a single dose of 35, 70, or 105 mg TMZ-modified release tablets (six subjects each). Pharmacokinetic evaluations and safety analysis were performed before the first dose and till 48 h post-first dose. Results Following administration of 35, 70, and 105 mg TMZ-modified release; the Cmax (mean±SD) was 79.32 (±23.08), 153.17 (±23.08), and 199.67 (±23.08) ng/mL, the Tmax was 5.42 (±0.49), 4.51 (±1.27), and 4.57 (±0.96) h, t1/2 was 7.75 (±1.62), 6.40 (±1.23), and 6.50 (±1.18) h, AUC(0-inf) was 1116.89 (±378.35), 1838.39 (±284.50), and 2504.84 (±348.35) ng.h/mL, CLR was 13.70 (±2.24), 14.80 (±5.91), and 19.58 (±6.24) L·h−1 and CL/F was 33.69 (±8.51), 38.85 (±6.15), and 42.74 (±7.10) L·h−1, respectively. Slope estimates for AUC(0-inf), AUC(0-t), and Cmax were less than 1. Corresponding 95% CI of the slope for the AUC parameters excluded 1, indicating that the deviation from dose-proportionality was statistically significant. Corresponding 95% CI of the slope for Cmax included 1, indicating that the less than dose-proportional increase in Cmax was not statistically significant. No significant adverse events were observed. Conclusion Substantial deviation from a dose-proportional increase in AUC(0-inf) and AUC(0-t) suggested a non-linear PK for TMZ-modified release. Single dose of TMZ-modified release was well tolerated and safe.

scholarly journals Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

2009 ◽  
Vol 53 (9) ◽  
pp. 3720-3725 ◽  
Author(s):  
Ann M. Ginsberg ◽  
Martino W. Laurenzi ◽  
Doris J. Rouse ◽  
Karl D. Whitney ◽  
Melvin K. Spigelman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Dose ◽  
Healthy Subjects ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Blood Levels ◽  
Drug Resistant ◽  
Single Dose Study ◽  
Multiple Dose Study ◽  
Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

scholarly journals A Phase 1, Randomized Ascending Single-Dose Study of Antagonist Anti-Human CD40 ASKP1240 in Healthy Subjects

2013 ◽  
Vol 13 (4) ◽  
pp. 1040-1046 ◽  
Author(s):  
R. Goldwater ◽  
J. Keirns ◽  
P. Blahunka ◽  
R. First ◽  
T. Sawamoto ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Phase 1 ◽  
Single Dose Study ◽  
Dose Study

Effects of Nondirective Suggestions on Pain Tolerance, Pain Threshold and Pain Intensity Perception

1997 ◽  
Vol 84 (3) ◽  
pp. 963-966 ◽  
Author(s):  
W. Neumann ◽  
H. Seelbach ◽  
J. Kugler ◽  
G. M. Krüskemper
Keyword(s):  
Pain Intensity ◽  
Healthy Subjects ◽  
Pain Threshold ◽  
General Information ◽  
Pain Tolerance ◽  
The Other ◽  
Information Cues ◽  
Intensity Perception ◽  
Pressure Algometer ◽  
Maximum Pain

In this experiment, we followed the issue whether nondirective suggestions have an effect on pain threshold, pain tolerance, and perception of pain intensity. 48 healthy subjects consented to take part. At intake into the study (t1), pain threshold and pain tolerance were assessed in all subjects using a pressure algometer. Perception of maximum pain intensity perception was rated on a scale of 0 to 25. Seven days later, the session was repeated (t2). Subjects were randomly assigned to one of two groups. One group received nondirective suggestions as pretreatment. Subjects listened to a tape of 20 min. which consisted of general information about pain theory. In this context, suggestions for coping with pain were placed. The other group served as a control and received no pretreatment. Analysis showed that pain tolerance was significantly prolonged in the group who received nondirective suggestions, while pain threshold and perception of maximum pain intensity did not differ across groups. This study demonstrates that nondirective suggestions are effective in prolonging pain tolerance. It can be stated that, beside information, cues on coping with pain may be helpful in clinical practice.

scholarly journals Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin.

1997 ◽  
Vol 41 (6) ◽  
pp. 1298-1300 ◽  
Author(s):  
N R Cutler ◽  
J Vincent ◽  
S S Jhee ◽  
R Teng ◽  
T Wardle ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Dose ◽  
Bacterial Meningitis ◽  
Intravenous Infusion ◽  
Healthy Subjects ◽  
Serum Samples ◽  
Single Dose Study ◽  
Dose Study ◽  
Mean Concentration ◽  
Time Point

A single-dose study was conducted to determine concentrations of trovafloxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects were administered single doses of alatrofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were taken from each subject at the time of CSF collection. A mean concentration of 5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans.

Sign in / Sign up

Export Citation Format

Share Document