scholarly journals Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function

2019 ◽  
Vol 9 (6) ◽  
pp. 699-708 ◽  
Author(s):  
Daisuke Miyatake ◽  
Tomohisa Shibata ◽  
Junko Toyoshima ◽  
Yuichiro Kaneko ◽  
Kazuo Oda ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Hepatic Function ◽  
Impaired Hepatic Function ◽  
Japanese Subjects

scholarly journals FRI0161 PHARMACOKINETICS AND SAFETY OF A SINGLE ORAL DOSE OF PEFICITINIB (ASP015K) IN SUBJECTS WITH NORMAL AND IMPAIRED HEPATIC FUNCTION

2019 ◽  
Author(s):  
Daisuke Miyatake ◽  
Tomohisa Shibata ◽  
Junko Toyoshima ◽  
Yuichiro Kaneko ◽  
Kazuo Oda ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Hepatic Function ◽  
Impaired Hepatic Function

scholarly journals Absolute Bioavailability of Esaxerenone and Food Effects on its Pharmacokinetics After a Single Oral Dose in Healthy Japanese Subjects: An Open-Label Crossover Study

2019 ◽  
Vol 36 (7) ◽  
pp. 1618-1627 ◽  
Author(s):  
Akifumi Kurata ◽  
Hidetoshi Furuie ◽  
Tomoko Ishizuka ◽  
Takafumi Nakatsu ◽  
Takako Shimizu ◽  
...  
Keyword(s):  
Oral Dose ◽  
Crossover Study ◽  
Single Oral Dose ◽  
Absolute Bioavailability ◽  
Food Effects ◽  
Open Label ◽  
Japanese Subjects

Influence of mild and moderate hepatic impairment on the pharmacokinetics (PK) of the pan-HER inhibitor dacomitinib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2568-2568 ◽  
Author(s):  
Nagdeep Giri ◽  
Anna Plotka ◽  
Yali Liang ◽  
Tanya Boutros ◽  
Grace Ni ◽  
...  
Keyword(s):  
Liver Function ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Moderate Hepatic Impairment ◽  
Open Label ◽  
Post Dose ◽  
Normal Hepatic Function ◽  
Mild Impairment

2568 Background: Dacomitinib (D) is a highly selective irreversible small molecule inhibitor of the HER family of tyrosine kinases in clinical development for NSCLC.Prior clinical studies of D, which has minimal renal excretion (~3%), enrolled pts with protocol-defined adequate liver function. Liver metastases, leading to abnormal liver function tests, are common in pts with advanced cancer. This study evaluated the effect of hepatic impairment on PK and safety of D following a single oral dose in subjects with mild or moderate hepatic impairment. Methods: In this phase I, open-label, parallel group study, 25 subjects with either normal hepatic function (n=8) or mild (Child-Pugh A; n=8) or moderate (Child-Pugh B; n=9) hepatic impairment were administered a single, oral dose of D (30 mg). PK samples were collected at intervals up to 264 h post-dose and safety was assessed by laboratory abnormalities, physical examination, vital signs, ECGs, and AE monitoring. Analysis of variance was performed on natural log-transformed AUC and Cmaxto estimate adjusted mean differences between groups and 90% CIs, which were exponentiated to produce the adjusted GMR and 90% CI of the ratios. Results: GMR and 90% CI for AUCinf and Cmax (preliminary analyses) are listed.Mean D exposure (AUCinf and Cmax) was similar in subjects with normal hepatic function and those with mild impairment. Moderate hepatic impairment decreased D exposure by 15% and 20% for AUCinf and Cmax, respectively, vs normal hepatic function, but the 90% CI was relatively wide, and included 1. Plasma protein binding of D was similar in the 3 groups. No clinically significant treatment-related AEs were reported. Conclusions: Mean D exposure (AUCinf and Cmax) was similar in subjects with normal hepatic function and those with mild impairment. Mean D exposure appeared slightly lower in subjects with moderate impairment. Dose reduction of D in subjects with mild or moderate hepatic impairment may not be necessary. A single 30 mg dose of D was well tolerated in subjects with mild or moderate hepatic impairment. Clinical trial information: NCT01571388. [Table: see text]

scholarly journals Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects with Normal and Impaired Renal Function

2019 ◽  
Vol 40 (2) ◽  
pp. 149-159 ◽  
Author(s):  
Daisuke Miyatake ◽  
Tomohisa Shibata ◽  
Mai Shibata ◽  
Yuichiro Kaneko ◽  
Kazuo Oda ◽  
...  
Keyword(s):  
Renal Function ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Impaired Renal Function ◽  
Japanese Subjects

scholarly journals Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment

2017 ◽  
Vol 58 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Manabu Kato ◽  
Naoyuki Tajima ◽  
Takako Shimizu ◽  
Masahiro Sugihara ◽  
Kenichi Furihata ◽  
...  
Keyword(s):  
Renal Impairment ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Japanese Subjects

scholarly journals 731. Pharmacokinetics of Gepotidacin (GSK2140944) in Subjects with Hepatic Impairment

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S327-S327
Author(s):  
Jonathan T Hands ◽  
Yu Tao ◽  
Courtney Tiffany ◽  
Caroline R Perry ◽  
Etienne Dumont ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Hepatic Impairment ◽  
Geometric Mean ◽  
Hepatic Clearance ◽  
Hepatic Function ◽  
Major Route ◽  
Bacterial Replication

Abstract Background Gepotidacin (GEP), a first in class novel triazaacenaphthylene bacterial topoisomerase inhibitor, inhibits bacterial replication and has in vitro and in vivo efficacy activity against key pathogens, including drug-resistant strains, associated with a range of infections. In a previous absorption, distribution, metabolism, and excretion study for GEP, the mean recovery of radioactivity in urine and feces accounted for approximately 31.2% and 52.5%, respectively, of [14C]-GEP administered as a single oral dose. GEP was eliminated mainly as parent in urine, accounting for approximately 20% of the administered dose. Elimination via metabolism accounted for a total of 13% to 19% of the dose. Average total intravenous clearance of approximately 43 L/hour and renal clearance (CLr) of approximately 16 L/hour provides a hepatic clearance of 27 L/hour, suggesting that hepatic clearance is a major route of elimination of GEP. Methods Participants with normal and varying degrees of hepatic impairment (HI) received a single oral dose of GEP 1,500 mg. PK collections of blood, urine and saliva were performed. Results Relative to normal hepatic function, GEP Cmax and AUC(0-∞) in plasma were increased by 1.2-fold in subjects with moderate, and between 1.7-fold to 1.9-fold in severe HI. The fraction of dose excreted in urine increased with an increase in hepatic impairment. GEP urine concentrations remained high over a 12-hour period. Saliva concentrations displayed a linear relationship with plasma (both total and unbound) concentrations (R2 = 0.76). The geometric mean ratio of saliva AUC to unbound plasma AUC values ranged from 0.746 to 0.839 across all groups. Administration of 1,500 mg oral GEP was generally tolerated. Conclusion An increase in the dosing interval or dose reduction may be required in patients with severe hepatic impairment. Disclosures All authors: No reported disclosures.

scholarly journals P291 Pharmacokinetics, safety, and tolerability of etrasimod (APD334) in subjects with mild, moderate, or severe hepatic impairment: a single-dose, open-label, parallel-group study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S321-S322
Author(s):  
C Lee ◽  
Y Tang ◽  
C Schroeder ◽  
J Zhang ◽  
T Nguyen-Cleary ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Normal Control ◽  
Hepatic Impairment ◽  
Hepatic Function ◽  
Control Groups ◽  
Severe Hepatic Impairment ◽  
Open Label ◽  
Mean Values

Abstract Background Etrasimod is an oral, selective sphingosine 1-phosphate receptor modulator in clinical development for immune-mediated inflammatory disorders, including ulcerative colitis, Crohn’s disease, and eosinophilic esophagitis. The objective of this study was to evaluate the effect of hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of etrasimod. Methods This single-dose, open-label, parallel-group study included 36 adult subjects (aged 18-80 years; body mass index ≥18 kg/m2) with hepatic impairment, based on Child-Pugh score at screening (mild=5 to 6 [n=8], moderate=7 to 9 [n=8], severe=10 to 14 [n=6]), and their demographically matched control subjects with normal hepatic function (n=14 total). The first subject with severe hepatic impairment was enrolled after ≥2 subjects with mild and ≥2 subjects with moderate hepatic impairment had been enrolled and followed for ≥48 hours after dosing to ensure no observed significant safety signals. On Day 1, subjects received a single oral dose of etrasimod 2 mg after a ≥10 hour fast. PK and safety data were collected over a 21-day follow-up period. Results Thirty-six subjects were enrolled and dosed; 35 subjects completed the study. When compared with their respective demographically matched normal control groups, single dose etrasimod peak exposure (Cmax) was comparable for all hepatic impairment groups, whereas etrasimod total exposure (AUC) measures were progressively higher (up to 57.3% higher) in the mild, moderate, and severe hepatic impairment groups (Table 1). Unbound etrasimod Cmax values were progressively lower (up to 42.0% lower) in the mild, moderate, and severe hepatic impairment groups, whereas unbound etrasimod AUC values were typically comparable for all hepatic impairment groups, when compared with their respective demographically matched normal control groups (Table 2). Etrasimod t1/2 only moderately increased as hepatic function decreased, with mean values ranging from 43.9 to 59.5 hours in the demographically matched normal control groups and mean values of 55.7, 69.7, and 76.5 hours in the mild, moderate, and severe hepatic impairment groups, respectively. A single oral dose of etrasimod 2 mg was well tolerated; there were no clinically significant safety findings when administered to subjects with normal hepatic function or subjects with mild, moderate, or severe hepatic impairment. Conclusion A single oral dose of etrasimod 2 mg was well tolerated, with relatively modest changes in etrasimod exposure observed in subjects with mild, moderate, or severe hepatic impairment. These results suggest that etrasimod dose adjustment may not be warranted in subjects with hepatic impairment.

A Rapid (48 hours) Thyroid Suppression Test using a Single Oral Dose of 100 of Triiodothyronine

1973 ◽  
Vol 12 (03) ◽  
pp. 218-224
Author(s):  
Elli Lakka - Papadodima ◽  
Constantin Ntalles ◽  
Denis Ikkos
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Suppression Test

Des mesurages répétés de la fixation thyroïdienne de 10 minutes du 132I injecté intraveineusement on été effectués sur 55 malades euthyroïdiens sans et avec goitre et sur 16 malades hyperthyreoïdiens par 4 jours consécutifs. Immédiatement après le premier mesurage tous les malades recevaient une dose unique oral de 100 μg de Triiodothyronine (T3). Les valeurs de fixation 24, 48 et 72 heures après le T3 (moyen ± déviation standard) étaient de 75 ± 1,7, 64 ± 1,8, et 67 ± 1,9 dans le groupe euthyroïdien et le 106 ± 2,6, 104 ± 2,2 et 108 ± 4,0 dans le groupe hyperthyroïdien, exprimés en pourcentage du groupe controle. 48 heures après T3 tous les personnes euthyroïdiens, sauf une, avaient des valeurs en dessous de 88% tandis que la valeur la plus basse des personnes hyperthyroïdiens ce jour était de 93%. La séparation des valeurs 48 heures des deux groupes était complète après avoir respecté l’influence de la première fixation sur la valeur 48 heures. On peut donc supposer q’un test thyroïdien de suppression utilisable en clinique peut-être effectué en 48 heures après une administration oral de 100 μg de T3 et mesurage de la fixation 10 minutes après l’injection du radioisotope.

Effect of Aspirin on the Thrombelastogram of Human Blood

1973 ◽  
Vol 30 (03) ◽  
pp. 494-498 ◽  
Author(s):  
G de Gaetano ◽  
J Vermylen
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Platelet Function ◽  
Human Blood ◽  
Platelet Rich Plasma ◽  
Plasma Samples ◽  
Release Reaction ◽  
Platelet Release

SummaryThrombelastograms of both native blood and re-calcified platelet-rich plasma samples taken from subjects given a single oral dose of aspirin (1 gram) were not significantly different from the pretreatment recordings. Aspirin also did not modify the thrombelastogram when preincubated in vitro with platelet-rich plasma at concentrations inhibiting the platelet “release reaction” by collagen. Thrombelastography therefore cannot evaluate the effect of aspirin on platelet function.

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