Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors

2012 ◽  
Vol 9 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Xian-Huo Wang ◽  
Shi-Yong Zhou ◽  
Zheng-Zi Qian ◽  
Hui-Lai Zhang ◽  
Li-Hua Qiu ◽  
...  
Keyword(s):  
Single Dose ◽  
Solid Tumors ◽  
Ursolic Acid ◽  
Healthy Adult ◽  
Advanced Solid Tumors ◽  
Adult Volunteers

The Single-Dose Pharmacokinetics of Clopidogrel in Healthy Adult Volunteers

2003 ◽  
Vol 73 (2) ◽  
pp. P47-P47
Author(s):  
J. Grenier ◽  
S. Ciric ◽  
J. Curry ◽  
G. Morelli ◽  
A. Arseneault ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Adult ◽  
Adult Volunteers

scholarly journals A Phase I Trial to Evaluate the Multiple-Dose Safety and Antitumor Activity of Ursolic Acid Liposomes in Subjects with Advanced Solid Tumors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zhengzi Qian ◽  
Xianhuo Wang ◽  
Zheng Song ◽  
Huilai Zhang ◽  
Shiyong Zhou ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Solid Tumors ◽  
Ursolic Acid ◽  
Multiple Dose ◽  
Day Treatment ◽  
The Body ◽  
Pharmacokinetic Analysis ◽  
Advanced Solid Tumors ◽  
Grade 3 ◽  
Multiple Dose Pharmacokinetics

Ursolic acid liposome (UAL), a new antitumor drug, has potential therapeutic value. However, limited clinical data exists regarding multiple-dose safety, antitumor activity, and the recommended dose (RD) of UAL for subjects with advanced solid tumors. All subjects were intravenously administered UAL for 14 consecutive days of a 21-day treatment cycle. Twenty-one subjects were enrolled in 1 of 3 sequential cohorts (56, 74, and 98 mg/m2) to evaluate multiple-dose tolerability and efficacy. Eight additional subjects were treated with UAL (74 mg/m2) to evaluate multiple-dose pharmacokinetics. No ≥grade 3 adverse events (NCI-CTC) were observed. Sixty percent subjects achieved stable disease after 2 treatment cycles. Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body. This trial demonstrates that UAL was tolerable, had manageable toxicity, and could potentially improve patient remission rates. A large phase II study is recommended to confirm these results (i.e., RD of 98 mg/m2).

First-in-human phaseⅠstudy of JPH203 in patients with advanced solid tumors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 419-419 ◽  
Author(s):  
Naohiro Okano ◽  
Kirio Kawai ◽  
Yoshiya Yamauchi ◽  
Takaaki Kobayashi ◽  
Daisuke Naruge ◽  
...  
Keyword(s):  
Amino Acids ◽  
Single Dose ◽  
Phase I ◽  
Disease Control ◽  
Solid Tumors ◽  
Phase I Study ◽  
Critical Role ◽  
Maximum Tolerated Dose ◽  
Cancer Growth ◽  
Advanced Solid Tumors

419 Background: Uptake of amino acids is essential for cancer growth. L-type amino acid transporter-1 (LAT-1) is overexpressed in various cancers, and uptake of LAT-1 substrate amino acids is known to have a critical role in cancer growth. JPH203 is a novel, selective, LAT-1 inhibitor. A first-in-human phase I study of JPH203 was designed to determine the safety, maximum-tolerated dose (MTD) and recommended dose. This study included evaluation of the anti-tumor effect, pharmacokinetics, and pharmacodynamics of JPH203 and analyzed plasma free amino acids. Methods: JPH203 was administered intravenously for 7 days followed by 21 days’ rest at planned doses ranging from 12 to 110 mg/m2 in patients with advanced solid tumors refractory to standard therapy. Before starting this schedule, we confirmed safety of a single dose of JPH203. Dose-limiting toxicity was evaluated during the first cycle, using a 3+3 design. Results: 17 patients were enrolled from January 2015 to August 2016. One patient was discontinued after a single dose of JPH203 because of tumor progression. Dosage was escalated up to 85 mg/m2. Grade 3 liver dysfunction occurred in 1 of 6 patients at 60 mg/m2 and in the first patient at 85 mg/m2. Therefore, it was determined that MTD was 60 mg/m2. Common treatment-related adverse events were increased ALT/AST, malaise, nausea, hypertension and fever of Grade 1 or 2. Partial response was achieved in a patient with biliary tract cancer (BTC) who continued JPH203 for two years without progression. Disease control (PR+SD) was observed in 3 of 5 patients with BTC and 2 of 6 with colorectal cancer. LAT-1 substrate amino acids and branched chain amino acids including LAT-1 substrate amino acids were higher in patients with BTC than in those with other cancers. All patients with disease control had a body mass index more than the median of 20.5 kg/m2. In exploratory analysis, longer survival was achieved in patients with high inhibition of uptake of LAT-1 substrate amino acids, compared with patients with low inhibition of uptake. Conclusions: JPH203 was well tolerated, resulting in promise against BTC. This phase I study suggested that LAT-1 could be targeted in treatment for advanced BTC, because LAT-1 substrate amino acids in plasma tended to remain high. Clinical trial information: UMIN000016546.

Phase I Clinical Study of AZD2171, an Oral Vascular Endothelial Growth Factor Signaling Inhibitor, in Patients With Advanced Solid Tumors

2007 ◽  
Vol 25 (21) ◽  
pp. 3045-3054 ◽  
Author(s):  
Joachim Drevs ◽  
Patrizia Siegert ◽  
Michael Medinger ◽  
Klaus Mross ◽  
Ralph Strecker ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Single Dose ◽  
Growth Factor ◽  
Phase I ◽  
Liver Metastases ◽  
Solid Tumors ◽  
Vascular Endothelial ◽  
Advanced Solid Tumors ◽  
Once Daily ◽  
Endothelial Growth Factor

Purpose AZD2171 is a highly potent oral selective inhibitor of vascular endothelial growth factor (VEGF) signaling. This phase I study was designed to evaluate the safety and tolerability of increasing doses of AZD2171, with additional assessments of pharmacokinetics, pharmacodynamics, and efficacy. Patients and Methods In part A, 36 patients with solid tumors and liver metastases refractory to standard therapies received once-daily oral AZD2171 (0.5 to 60 mg). Doses were escalated in successive cohorts until the maximum-tolerated dose was identified. In part B, patients with (n = 36) or without (n = 11) liver metastases were randomly assigned to receive once-daily AZD2171 (20, 30, or 45 mg). In both parts, treatment continued until tumor progression or dose-limiting toxicity (DLT) was observed. Results Eighty-three patients received AZD2171, which was generally well tolerated at doses of 45 mg/d or less; the most frequently reported dose-related adverse events were diarrhea, dysphonia, and hypertension. The most common DLT was hypertension (n = 7), which occurred at AZD2171 doses of 20 mg and higher. After a single dose, maximum plasma (peak) drug concentration after single-dose administration (Cmax) was achieved 1 to 8 hours postdosing with an arithmetic mean half-life associated with terminal slope of a semilogarithmic concentration-time curve (t1/2λz) of 22 hours. Pharmacodynamic assessments demonstrated time-, dose-, and exposure-related decreases in initial area under the curve, defined over 60 seconds post-contrast arrival in the tissue (iAUC60) using dynamic contrast-enhanced magnetic resonance imaging, as well as dose- and time-dependent reductions in soluble VEGF receptor 2 levels. Preliminary evidence of efficacy included two confirmed partial responses and 22 patients with stable disease; effects on tumor size appeared to be dose related. Conclusion Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad range of advanced solid tumors.

Influence of Enteral Feedings on Phenytoin Sodium Absorption from Capsules

1988 ◽  
Vol 22 (2) ◽  
pp. 130-133 ◽  
Author(s):  
Lyn Y. Nishimura ◽  
Edward P. Armstrong ◽  
Patricia M. Plezia ◽  
Robert P. Iacono
Keyword(s):  
Single Dose ◽  
Healthy Adult ◽  
Relative Bioavailability ◽  
Sodium Absorption ◽  
Crossover Fashion ◽  
Phenytoin Sodium ◽  
Enteral Feedings ◽  
Blood Specimens ◽  
Two Phases ◽  
Adult Volunteers

The influence of enteral feedings (with Ensure) on the absorption of phenytoin sodium from capsules was studied. Six healthy adult volunteers were given a single dose of phenytoin capsules 400 mg po on two occasions. Blood specimens were collected for 48 hours after each dose. In a randomized, crossover fashion, each subject completed the following two phases: (1) phenytoin without enteral feedings, and (2) concomitant enteral feedings before phenytoin and continued at 100 ml/h for ten hours. The areas under the concentration versus time curves from 0-48 hours (AUCo-48) were not significantly different between the two phases (p > 0.5). The percent relative bioavailability of phenytoin with enteral feedings was 101.7 percent. This study suggests that enteral feedings do not affect the serum concentrations of phenytoin after a single dose given in capsule form.

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