scholarly journals Safety, tolerability, and pharmacokinetics of single‐ and multiple‐dose administration of islatravir (MK‐8591) in adults without HIV

2021 ◽  
Author(s):  
Randolph P. Matthews ◽  
Wendy Ankrom ◽  
Evan Friedman ◽  
Deanne Jackson Rudd ◽  
Yang Liu ◽  
...  
Keyword(s):  
Multiple Dose ◽  
Dose Administration ◽  
Multiple Dose Administration

scholarly journals Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects

2013 ◽  
Vol 76 (5) ◽  
pp. 763-775 ◽  
Author(s):  
José Francisco Rocha ◽  
Luis Almeida ◽  
Amílcar Falcão ◽  
P. Nuno Palma ◽  
Ana I. Loureiro ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Multiple Dose ◽  
Dose Administration ◽  
Multiple Dose Administration ◽  
Long Acting

P1-229: Population pharmacokinetic modeling of the novel BACE inhibitor MK-8931 following single and multiple dose administration in healthy subjects

2012 ◽  
Vol 8 (4S_Part_5) ◽  
pp. P187-P187
Author(s):  
Lei Ma ◽  
Marissa Dockendorf ◽  
Gopal Krishna ◽  
Huub-Jan Kleijn ◽  
Jing Su ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Multiple Dose ◽  
Pharmacokinetic Modeling ◽  
Population Pharmacokinetic ◽  
The Novel ◽  
Dose Administration ◽  
Population Pharmacokinetic Modeling ◽  
Multiple Dose Administration ◽  
Bace Inhibitor

scholarly journals Comparative pharmacokinetics of amphotericin B after single- and multiple-dose administration of G-ABCD and conventional amphotericin B deoxycholate to rats

2020 ◽  
Vol 22 ◽  
pp. 608-612
Author(s):  
Huanhuan Qi ◽  
Xueyuan Zhang ◽  
Hao Feng ◽  
Yating Xiong ◽  
Yuancheng Chen ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Multiple Dose ◽  
Dose Administration ◽  
Multiple Dose Administration ◽  
Amphotericin B Deoxycholate

scholarly journals No Pharmacokinetic Drug-Drug Interaction Between Prasugrel and Vorapaxar Following Multiple-Dose Administration in Healthy Volunteers

2017 ◽  
Vol 7 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Matt S. Anderson ◽  
Teddy Kosoglou ◽  
Paul Statkevich ◽  
Jing Li ◽  
Jennifer Rotonda ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Healthy Volunteers ◽  
Multiple Dose ◽  
Dose Administration ◽  
Multiple Dose Administration ◽  
Drug Drug Interaction ◽  
Pharmacokinetic Drug

Single and Multiple Oral Doses of LGD-4665, a Small Molecule Thrombopoietin Receptor Agonist, Increase Platelet Counts in Healthy Male Subjects

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1298-1298 ◽  
Author(s):  
Zofia E. Dziewanowska ◽  
Richard M. Matsumoto ◽  
J.K. Zhang ◽  
Kristine Schindler ◽  
Gordon Loewen ◽  
...  
Keyword(s):  
Platelet Count ◽  
Single Dose ◽  
Multiple Dose ◽  
Receptor Agonist ◽  
Healthy Male ◽  
Post Dose ◽  
Dose Administration ◽  
Platelet Counts ◽  
Multiple Dose Administration ◽  
Male Subjects

Abstract LGD-4665, an oral thromobopoietin receptor agonist, is being developed as a new generation small molecule thrombopoietin (TPO) mimetic. LGD-4665 is a highly selective and potent agonist of the TPO receptor and induces differentiation and proliferation of megakaryocytes. A single-center, randomized, placebo-controlled, double-blind, escalating dose group study was conducted to assess the pharmacodynamics, pharmacokinetics (PK), and safety of LGD-4665 in healthy male subjects after single and multiple doses. In the single dose phase of the study, 5 dose cohorts of 6 subjects each were randomized at a ratio of 2:1 (LGD-4665: Placebo). LGD-4665 doses of 1, 5, 10, 20, and 40 mg were escalated sequentially. In the multiple dose phase, 8 subjects received 5 mg of study drug or placebo at a ratio of 3:1, respectively, once daily for 14 days. Clinical assessments were conducted for 21 and 35 days following treatment initiation in the single and multiple dose phases, respectively. Platelet count increases were determined as the maximal observed increase in post-dose platelet value relative to baseline, expressed both as absolute value and percent increase. Following single dose administration, a statistically-significant (p=0.011) platelet count increase compared to placebo was observed following a 40 mg LGD-4665 dose. In subjects receiving this dose, individual maximum increases in platelet counts ranged between 53 and 83 x1000/μL (mean = 65 x1000/μL; 29% increase from baseline). Following multiple dose administration of 5 mg daily for 14 days, increases in platelet counts over baseline were observed in all drug-treated subjects (n=6) with a mean maximal increase from baseline of 43%. From PK measurements, a dose-proportional increase in systemic exposure after single doses of LGD-4665 was observed among the dose groups. Mean area-under-the-curve from time zero to infinity (AUC0-inf) increased from 2.88 to 155 μg·h/mL following single doses of 1 to 40 mg, respectively, with AUC0–24h values of 0.43 – 25.3 μg·h/mL. Maximum LGD-4665 concentrations (Cmax) increased from 0.029 to 1.56 μg/mL following administration of 1 to 40 mg single doses, respectively. In the multiple phase, 5 mg daily doses for 14 days resulted in a mean Cmax of 0.83 μg/mL and the Cmax were reached at 4 hours post dose. The mean steady-state AUC0 to 24h was 17.4 μg·h/mL. Overall, LGD-4665 was safe and well tolerated at all dose levels tested during both phases of the study. All AEs were appraised as mild to moderate. The majority of AEs were not related to LGD-4665 and no apparent dose-relationship was observed. No serious AEs were reported. No subjects discontinued the study due to AEs. No clinically significant laboratory abnormalities, effects on electrocardiograms and vital signs were observed. In summary, LGD-4665 increase platelet counts following single and multiple dose administration and was well tolerated.

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