scholarly journals Studies on the disposion of (14C)NB-506: Plasma Concentration-Time Profile, Distribution, Metabolism and Excretion of (14C)NB-506 after Single and Repeated Intravenous Administration in Rats.

1998 ◽  
Vol 13 (4) ◽  
pp. 337-345
Author(s):  
Mikio ISHII ◽  
Norihiro TAKENAGA ◽  
Hiroyuki ISHIZAKI ◽  
Toshio KAMEI ◽  
Shin-ichi NINOMIYA ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Intravenous Administration ◽  
Time Profile ◽  
Concentration Time ◽  
Profile Distribution

Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS, the First Selective Small Molecule Calcitonin Gene-Related Peptide Receptor Antagonist, Following Single Intravenous Administration in Healthy Volunteers

Cephalalgia ◽  
2004 ◽  
Vol 24 (8) ◽  
pp. 645-656 ◽  
Author(s):  
M Iovino ◽  
U Feifel ◽  
C-L Yong ◽  
J-M Wolters ◽  
G Wallenstein
Keyword(s):  
Plasma Concentration ◽  
Receptor Antagonist ◽  
Small Molecule ◽  
Intravenous Administration ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Concentration Time ◽  
Calcitonin Gene ◽  
Dose Levels ◽  
Single Intravenous Administration

BIBN 4096 BS ([R-(R∗,S∗)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.

scholarly journals Predicting Method for the Human Plasma Concentration–Time Profile of a Monoclonal Antibody from the Half-life of Non-human Primates

2020 ◽  
Vol 43 (5) ◽  
pp. 823-830 ◽  
Author(s):  
Genki Nakamura ◽  
Kazuhisa Ozeki ◽  
Miho Nagayasu ◽  
Takeru Nambu ◽  
Takayuki Nemoto ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Plasma Concentration ◽  
Human Plasma ◽  
Half Life ◽  
Time Profile ◽  
Concentration Time

scholarly journals Comparison of Dissolution Profile and Plasma Concentration-time Profile of the Thalidomide Formulations Made by Japanese, Mexican and British Companies

2008 ◽  
Vol 128 (10) ◽  
pp. 1449-1457 ◽  
Author(s):  
Yukiyoshi FUJITA ◽  
Koujirou YAMAMOTO ◽  
Tohru AOMORI ◽  
Hirokazu MURAKAMI ◽  
Ryuya HORIUCHI
Keyword(s):  
Plasma Concentration ◽  
Time Profile ◽  
Dissolution Profile ◽  
Concentration Time

scholarly journals Effects of Intestinal Microecology on Metabolism and Pharmacokinetics of Oral Wogonoside and Baicalin

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Shihua Xing ◽  
Mengyue Wang ◽  
Ying Peng ◽  
Xiaobo Li
Keyword(s):  
Plasma Concentration ◽  
Herbal Medicine ◽  
Intestinal Microbiota ◽  
Time Profile ◽  
Flavonoid Glycosides ◽  
Pharmacokinetic Parameters ◽  
Clinical Use ◽  
Scutellaria Baicalensis Georgi ◽  
Concentration Time ◽  
The Difference

Baicalin and wogonoside are two of the most abundant flavonoid glycosides in the root of Scutellaria baicalensis Georgi, which is a widely used peroral herbal medicine with anticancer, antiviral, antibacterial and anti-inflammatory properties. In the present study, the effects of intestinal microecology on the metabolism and pharmacokinetics of orally administered baicalin and wogonoside were investigated by UPLC-QTOF/MS measurement of the difference in metabolites between normal and antibiotic-pretreated rats. In the antibiotic-pretreated rats, the plasma concentration-time profile and pharmacokinetic parameters of the two flavonoid glycosides and their relevant aglycone forms were significantly changed compared with those in normal rats. Further, hydrolysis and glucuronidated metabolites were not detected in the cecum contents and urine samples from antibiotic-pretreated rats. These results suggested that intestinal microbiota may play a key role in the pharmacokinetics and metabolism of peroral baicalin and wogonoside. According to our findings, it is recommended that the root of S. baicalensis should not be co-administered with antibiotics in clinical use.

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