Dose dependent pharmacokinetics of nitroglycerin after multiple intravenous infusions in healthy volunteers

1985 ◽  
Vol 13 (2) ◽  
pp. 143-157 ◽  
Author(s):  
Patrick K. Noonan ◽  
Roger L. Williams ◽  
Leslie Z. Benet
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Infusions ◽  
Multiple Intravenous Infusions ◽  
Dose Dependent

scholarly journals 380 GS-3583, a novel FLT3 agonist Fc fusion protein, expands conventional dendritic cells in healthy volunteers

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A413-A414
Author(s):  
Nishanthan Rajakumaraswamy ◽  
Anees Dauki ◽  
Michelle Kuhne ◽  
Torsten Trowe ◽  
Winnie Weng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Fusion Protein ◽  
Healthy Volunteers ◽  
Phase 1 ◽  
Vital Role ◽  
Controlled Study ◽  
Therapeutic Effects ◽  
Fc Fusion Protein ◽  
Quantitative Changes ◽  
Dose Dependent

BackgroundConventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor specific CD8+ T cells and their recruitment to tumor microenvironment (TME). However, cDC1s are often underrepresented in the TME. Systemic administration of Fms-like tyrosine kinase 3 ligand (FLT3L), a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to expansion of cDC1s in the periphery which can then be recruited into the TME. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T cell mediated anti-tumor activity. We sought to evaluate the pharmacodynamic (PD) effect of a single dose of GS-3583 in healthy volunteers alongside its safety. Herein, we present the updated results of the study.MethodsThis was a first-in-human, placebo-controlled study of GS-3583 in healthy volunteers to evaluate the safety, pharmacokinetics (PK), and PD of escalating single doses (ranging from 75 micrograms to 2000 micrograms) of GS-3583. The study was blinded to the subjects and the investigator. Each dose cohort enrolled 8–12 healthy subjects who received GS-3583 or placebo as single IV infusion at 3:1 ratio. Subjects were observed in the phase 1 unit for 15 days and then for 12 weeks as outpatients. As part of the PD evaluation, we investigated the changes in the number of cDC1 and cDC2 cells.ResultsAs of 2nd July 2021, selected safety, PK and PD data from all 4 cohorts were available. GS-3583 was well tolerated and all subjects had been discharged. To date, there have been no serious or grade 3 or higher adverse events. Preliminary PK analysis suggested dose-dependent increase in GS-3583 exposure (AUC and Cmax). Preliminary PD analysis shows that administration of GS-3583 resulted in temporary, dose-dependent increases in cDC1/cDC2 cells that peaked between days 5–11 (higher doses resulted in later peaks) and returned to baseline within 3 weeks of drug administration (table 1, figure 1).Abstract 380 Table 1Selected subject characteristics and pharmacodynamic resultsAbstract 380 Figure 1A) Comparison of cDC1 cell quantitative changes in cohorts 1–4; B) Comparison of cDC2 cell quantitative changes in cohorts 1–4ConclusionsGS-3583 infusion was well tolerated and induced dose dependent expansion of dendritic cells in the periphery in healthy volunteers. In patients with cancer, this increase in dendritic cells can be utilized to enhance anti-tumor therapeutic effects of immuno-oncology therapies.AcknowledgementsFunding provided by Gilead Sciences, Inc.Ethics ApprovalThe study received study site IRB/Ethics Committee approval prior to enrollment of subjects.

Time taken for safe manual intravenous infusions of up to 100 ml saline to healthy volunteers

2001 ◽  
Vol 15 (5) ◽  
pp. 227-229
Author(s):  
M.V. Cantarini ◽  
G. Hooper ◽  
R.M. Braybrooke ◽  
J.A. Lockton ◽  
A.M. Hughes
Keyword(s):  
Healthy Volunteers ◽  
Intravenous Infusions

Dose-dependent gastrointestinal effects of the somatostatin analog lanreotide in healthy volunteers

1999 ◽  
Vol 65 (4) ◽  
pp. 413-419 ◽  
Author(s):  
J DREWE ◽  
C SIEBER ◽  
C MOTTET ◽  
C WULLSCHLEGER ◽  
F LARSEN ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Somatostatin Analog ◽  
Dose Dependent

scholarly journals Dose-Dependent Inhibition of the CYP2D6 Catalyzed Oxidation of Sparteine by Mepyramine in Healthy Volunteers

2001 ◽  
Vol 89 (6) ◽  
pp. 331-334 ◽  
Author(s):  
Selim Kortunay ◽  
Atila Bozkurt ◽  
Nursabah E. Basci ◽  
Kim Brosen ◽  
S. Oguz Kayaalp
Keyword(s):  
Healthy Volunteers ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Catalyzed Oxidation

scholarly journals Dose-dependent Effects of Smoked Cannabis on Capsaicin-induced Pain and Hyperalgesia in Healthy Volunteers

2007 ◽  
Vol 107 (5) ◽  
pp. 785-796 ◽  
Author(s):  
Mark Wallace ◽  
Gery Schulteis ◽  
J Hampton Atkinson ◽  
Tanya Wolfson ◽  
Deborah Lazzaretto ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Drug Exposure ◽  
Pain Perception ◽  
Experimental Pain ◽  
High Dose ◽  
Significant Difference ◽  
Pain State ◽  
Double Blinded ◽  
Dose Dependent ◽  
Higher Doses

Background Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. Methods In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed. Results Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. Conclusions This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.

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