scholarly journals Safety, Pharmacokinetics, and Pharmacodynamics of Spectrum Yellow Oil in Healthy Participants

2021 ◽  
Author(s):  
Erica N Peters ◽  
Irina Mosesova ◽  
Laura MacNair ◽  
Ryan Vandrey ◽  
M Hunter Land ◽  
...  
Keyword(s):  
Subjective Effects ◽  
Dose Proportionality ◽  
Study Medication ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Limit Of Quantification ◽  
Treatment Groups ◽  
Multiple Dose Study ◽  
Dose Study ◽  
Urine Concentrations ◽  
Healthy Participants

Abstract Due to a lack of published pharmacokinetic (PK) and/or pharmacodynamic (PD) data, decision-making surrounding appropriate dosing of cannabis used for medical purposes is limited. This multiple-dose study evaluated the safety, tolerability, PK, and PD of Spectrum Yellow oil [20 mg/mL cannabidiol (CBD)/<1 mg/mL ∆9-tetrahydrocannabinol (THC)]. Participants (N=43) were randomized to one of five groups: 120 mg CBD and 5.4 mg THC daily, 240 mg CBD and 10.8 mg THC daily, 360 mg CBD and 16.2 mg THC daily, 480 mg CBD and 21.6 mg THC daily, or placebo. Study medication was administered every 12 hours for seven consecutive days. Treatment-emergent adverse events (TEAEs); plasma and urine concentrations of THC, CBD, and metabolites; and self-reported subjective effects were collected. Nearly all TEAEs (44/45) were of mild or moderate severity; none was serious. The highest incidence of TEAEs (67%) was in the two higher-dose treatment groups. The highest number of TEAEs (17/45) occurred on the first treatment day. Steady-state plasma CBD concentrations were reached by Day 7. On Day 7, CBD exposure showed dose-proportionality (AUC0-t slope=1.03 [0.70, 1.36], Cmax slope=0.92 [0.53, 1.31]). Most plasma THC concentrations were below the limit of quantification. Across Days 1 and 7, there were no consistent differences in subjective effects between placebo and active study medication. A prudent approach to improve tolerability with Spectrum Yellow oil might involve initial doses no higher than 240 mg total CBD and 10.8 mg total THC daily in divided doses, with titration upwards over time as needed based on tolerability.

A single- and multiple-dose study to investigate the pharmacokinetics and pharmacodynamics of opicapone, a novel COMT inhibitor, in rat

2017 ◽  
Vol 125 ◽  
pp. 146-155 ◽  
Author(s):  
Daniela Gonçalves ◽  
Gilberto Alves ◽  
Ana Fortuna ◽  
Maria João Bonifácio ◽  
Patrício Soares-da-Silva ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Comt Inhibitor ◽  
Multiple Dose Study ◽  
Dose Study

Safety, Tolerability and Pharmacokinetics of GMI-1070, a Pan-Selectin Inhibitor for Treatment of Vaso-Occlusive Crisis: Single and Multiple Dose Studies in Healthy Volunteers.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1526-1526 ◽  
Author(s):  
Yuli Xie ◽  
Rebecca Seufert ◽  
John L. Magnani ◽  
William Kramer ◽  
Helen M. Thackray
Keyword(s):  
Healthy Volunteers ◽  
Dose Regimen ◽  
Multiple Dose ◽  
Study Drug ◽  
Loading Dose ◽  
Employment Equity ◽  
Multiple Dose Study ◽  
Dose Study ◽  
Urine Concentrations ◽  
Equity Ownership

Abstract Abstract 1526 Poster Board I-549 Introduction GMI-1070 is a pan-selectin inhibitor which targets E-, P-, and L-selectin, and has demonstrated activity in multiple animal models of disease including sickle cell vaso-occlusive crisis, myocardial infarction, delayed-type hypersensitivity, and microcirculation in diabetes. These Phase 1 healthy volunteer studies evaluated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) GMI-1070 in single and multiple doses, using a dose-ranging design. Methods A total of 72 healthy volunteers were randomized to receive study drug (GMI-1070 or placebo) in two blinded studies. In the first study, subjects were enrolled in groups of 8 (at a 3:1 ratio), administered a single IV dose of the study drug, and evaluated for safety prior to a dose review by the investigator and medical monitor. After the safety data from each group of 8 was reviewed in a blinded fashion, the decision was made to advance to the next dose group. Doses evaluated in the study were 2, 5, 10, 20, and 40 mg/kg. In the second study, subjects were enrolled similarly in groups of 8 (at a 3:1 ratio), administered multiple IV doses of the study drug over the course of 2 to 4 days, and evaluated for safety and dose escalation in a similar fashion. Doses evaluated in the multiple dose study were: 5, 10, and 20 mg/kg q8 hours for 13 doses (4 days); and finally a loading dose regimen of 40 mg/kg followed by 20 mg/kg q8 hours for 6 doses (2 days). For both studies, safety parameters included adverse events (AEs), clinical lab results, vital signs, ECG, and physical exam. Plasma and urine concentrations of GMI-1070 were measured, and PK parameters were calculated using a non-compartmental analysis. Results All 72 randomized healthy volunteers were included in the safety analysis, and all 54 who received GMI-1070 were included in the PK analysis. There were no serious AEs in either study. All AEs in subjects receiving GMI-1070 were grades 1 or 2 (mild or moderate); no grade 3 (severe) AEs were seen in subjects receiving GMI-1070. One subject did exhibit a pruritic rash while receiving the loading dose regimen of the multiple dose study, and had to discontinue study drug after 3 doses. The rash resolved with treatment. All other AEs in all groups were either possibly related, probably not related, or unrelated to study drug. There was no treatment- or dose-related trend in the incidence of AEs. Overall, there also did not appear to be any clinically significant treatment- or dose-related trends in the clinical lab, vital sign, ECG, or physical exam data in either study. Analysis of the plasma and urine concentrations indicated linear PK over the range of doses tested. The elimination half life is 8 hours with the multiple dose regimen, with a minimum of 89% of the dose recovered in the urine. Conclusions GMI-1070, a pan-selectin inhibitor administered in single or multiple doses IV, at the doses used in these studies, appears to be safe and well-tolerated with linear PK. These studies support proceeding with evaluation of GMI-1070 in the treatment of sickle cell patients in vaso-occlusive crisis. Disclosures Xie: MDS Pharma Services: Employment. Seufert:GlycoMimetics, Inc.: Consultancy. Magnani:GlycoMimetics, Inc.: Employment, Equity Ownership. Kramer:GlycoMimetics, Inc.: Consultancy. Thackray:GlycoMimetics, Inc: Employment, Equity Ownership.

scholarly journals INFLUENCE OF LOVASTATIN ON PHARMACOKINETICS AND PHARMACODYNAMICS OF GLIPIZIDE IN HEALTHY AND STREPTOZOTOCIN - INDUCED DIABETIC RATS: INVOLVEMENT OF P-GLYCOPROTEIN INHIBITION

2016 ◽  
Vol 9 (5) ◽  
pp. 3
Author(s):  
Kishore Kumar Kadimpati ◽  
Vanishree Sammeta ◽  
Ravindra Babu Pingili ◽  
Dr. Sujatha Sanneboina
Keyword(s):  
Multiple Dose ◽  
Diabetic Rats ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Glycoprotein P ◽  
Multiple Dose Study ◽  
P Glycoprotein ◽  
Dose Study ◽  
Glycoprotein Inhibition ◽  
Everted Sacs

ABSTRACTThis study evaluated the effect of lovastatin (Lov) on the pharmacokinetics and pharmacodynamics of glipizide (Gpz) in healthy and streptozotocininduceddiabeticrats.In singledose study(SDS), blood samples werecollectedonthe 1st day, whereas in multiple dose study on the 15 day at0-12 hrs. Lov significantly altered the pharmacokinetic parameters at the dose of 15 mg/kg in SDS and multiple dose study. The C of Gpz wasincreased from 2.97 to 8.38 and 9.87 to 24.58 ng/mL in healthy and diabetic rats, respectively, in multiple dose study. Rat everted sacs were used tostudy the transport of Gpz in the presence of Lov and verapamil (P-glycoprotein [P-gp] inhibitor). The transport of Gpz from mucosal to the serosalsurface was significantly increased from 4.32 to 5.65 and 6.02 µg/mL in the presence of Lov and verapamil, respectively. The interaction between Lovand Gpz is due to P-gp and CYP2C9 inhibition.Keywords: Diabetes, Dyslipidemia, Glipizide, Lovastatin, P-glycoprotein.maxth

Comparison of flurbiprofen and acetaminophen with codeine in postoperative foot pain

1990 ◽  
Vol 80 (5) ◽  
pp. 266-270 ◽  
Author(s):  
ML Ottinger ◽  
KW Kinney ◽  
JR Black ◽  
M Wittenberg
Keyword(s):  
Multiple Dose ◽  
Rescue Medication ◽  
Codeine Phosphate ◽  
Foot Pain ◽  
Efficacy And Safety ◽  
Foot Surgery ◽  
Double Blind ◽  
Treatment Groups ◽  
Multiple Dose Study ◽  
Dose Study

The purpose of this double-blind, randomized, parallel, multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery. Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups. There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy. The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group.

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