Assessing Systemic Drug Exposure in Repeated Dose Toxicity Studies in the Case of Complete and Incomplete Sampling

2009 ◽  
pp. n/a-n/a
Author(s):  
Martin J. Wolfsegger ◽  
Thomas Jaki
Keyword(s):  
Drug Exposure ◽  
Repeated Dose ◽  
Toxicity Studies ◽  
Systemic Drug Exposure ◽  
Repeated Dose Toxicity ◽  
Incomplete Sampling ◽  
Systemic Drug

Oral Repeated-dose Toxicity Studies Especially in the Liver and Kidney of Rats Administered with Organic Germanium-fortified Yeasts

2006 ◽  
Vol 11 (2) ◽  
pp. 115-119 ◽  
Author(s):  
Sung-Hee Lee ◽  
Kyeong-Nam Oh ◽  
Sook-Nyung Rho ◽  
Bok-Hee Lee ◽  
Hyun-Joo Lee
Keyword(s):  
Repeated Dose ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity ◽  
Liver And Kidney

scholarly journals Intrathecal Riluzole for the Treatment of Patients With Amyotrophic Lateral Sclerosis

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Nicholas M Boulis
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Side Effects ◽  
Oral Administration ◽  
Oral Therapy ◽  
Drug Exposure ◽  
Oral Treatment ◽  
Oral Drug ◽  
Systemic Drug Exposure ◽  
Lateral Sclerosis ◽  
Systemic Drug

Abstract INTRODUCTION Oral riluzole is the only approved treatment known to improve survival in patients with amyotrophic lateral sclerosis (ALS), with modest efficacy and dosing limited by hepatic toxicity and asthenia. We postulated that a continuous intrathecal (IT) delivery of low daily doses of riluzole could elevate spinal cord (SC) concentrations well above those achievable with oral treatment alone, without increasing side-effects. METHODS A 6-wk and a 24-wk GLP study were conducted to evaluate the safety of IT riluzole in purpose-bred hound dogs. Oral riluzole, equivalent to 50 mg BID in humans, was administered in combination with one of 3 IT doses given through continuous infusion. Plasma, SC, and brain concentrations of riluzole were measured, along with assessments of safety and tolerability. RESULTS In the 6-wk study, when combining the oral and IT routes, IT infusion significantly increased SC concentrations well above those achieved with oral drug administration alone, without increasing brain concentrations. All IT doses in combination with oral administration were well tolerated by the animals. In the 6-mo study, the lowest dose used in the 6-wk study was dropped and a higher dose was added. This highest dose of IT riluzole was not tolerated by the dogs and yielded SC and brain concentrations significantly higher than achieved in any of our previous studies. CONCLUSION Continuous IT administration of riluzole when combined with oral administration can increase the SC concentration of riluzole above those achievable with oral therapy, without increasing the risk for adverse events associated with systemic drug exposure or off-target side-effects in the brain. Therefore, IT riluzole infusion when used in conjunction with oral therapy may safely enhance lower motor neuron neuroprotection and improve the survival benefit of the drug through enhanced SC delivery, and, with a careful selection of IT doses, it could be implemented in patients with ALS.

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

1988 ◽  
Vol 6 (1) ◽  
pp. 158-162 ◽  
Author(s):  
B Reichman ◽  
M Markman ◽  
T Hakes ◽  
N Kemeny ◽  
D Kelsen ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Infusion ◽  
Phase I Study ◽  
Clinical Utility ◽  
Phase I Trial ◽  
Drug Exposure ◽  
Continuous Intravenous Infusion ◽  
Future Studies ◽  
Systemic Drug Exposure ◽  
Systemic Drug

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

scholarly journals Oral repeated-dose toxicity studies of BIA 10–2474 in Wistar rat

2020 ◽  
Vol 111 ◽  
pp. 104540 ◽  
Author(s):  
A. Wallace Hayes ◽  
Jerry F. Hardisty ◽  
Stephen B. Harris ◽  
Yoshimasa Okazaki ◽  
Klaus Weber
Keyword(s):  
Wistar Rat ◽  
Repeated Dose ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity

Acute and repeated dose toxicity studies of recombinant saxatilin, a disintegrin from the Korean snake (Gloydius saxatilis)

Toxicon ◽  
2008 ◽  
Vol 51 (3) ◽  
pp. 406-417 ◽  
Author(s):  
Young-Doug Sohn ◽  
Sung-Yu Hong ◽  
Kil-Sang Cho ◽  
Won-Seok Choi ◽  
Si-Whan Song ◽  
...  
Keyword(s):  
Repeated Dose ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity

scholarly journals INTRAVENOUS SINGLE AND REPEATED DOSE TOXICITY STUDIES OF CIMADRONATE (YM175), A NOVEL BISPHOSPHONATE, IN RATS

1995 ◽  
Vol 20 (SupplementI) ◽  
pp. 15-26 ◽  
Author(s):  
Atsushi OKAZAKI ◽  
Hiroko SAKAI ◽  
Toshiaki MATSUZAWA ◽  
Chris J. PERKIN ◽  
Philip W. EAST
Keyword(s):  
Repeated Dose ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity

Neurobehavioural and repeated-dose toxicity studies on the extractive from the decoction of a mixture of Alstonia boonei and Picralima nitida in mice

2019 ◽  
Vol 29 (2) ◽  
pp. 375-383
Author(s):  
Clement O. Ajayi ◽  
Anthony A. Elujoba ◽  
Awodayo O. Adepiti ◽  
Ronald A. Bejide ◽  
Oluwole I. Adeyemi
Keyword(s):  
Repeated Dose ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity

scholarly journals Oral repeated-dose toxicity studies of BIA 10–2474 in cynomolgus monkeys

2020 ◽  
Vol 111 ◽  
pp. 104547 ◽  
Author(s):  
Klaus Weber ◽  
Rüdiger Häcker ◽  
Jerry F. Hardisty ◽  
Stephen B. Harris ◽  
A. Wallace Hayes
Keyword(s):  
Repeated Dose ◽  
Cynomolgus Monkeys ◽  
Toxicity Studies ◽  
Repeated Dose Toxicity
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