Pharmacokinetic Comparison of Sustained- and Immediate-Release Oral Formulations of Cilostazol in Healthy Korean Subjects: A Randomized, Open-Label, 3-Part, Sequential, 2-Period, Crossover, Single-Dose, Food-Effect, and Multiple-Dose Study

In a single-dose study, 18 healthy adult males consumed each of six dosage forms of theophylline. A conventional-release tablet, a syrup, and four competing brands of controlled-release theophylline were studied. Serial serum samples were obtained and analyzed via high pressure liquid chromatography (HPLC). After achieving steady state, 15 healthy adult males consumed each of five dosage forms of theophylline in a multiple-dose study. Serial blood samples were obtained between 0 and 72 hours and subjected to analysis with HPLC. The results indicated that the controlled-release products were not bioequivalent, although they achieved longer time-to-peak values than did the immediate-release syrup and the conventional-release tablet. A single sustained-release product was uniquely different on most pharmacokinetic parameters when compared with the remaining three controlled-release products. In general, the dosage form variation exceeded the individual subject variation on the single-dose study, but the opposite was true for the multiple-dose study.

Download Full-text

Pharmacokinetics of Rasagiline in Healthy Adult Chinese Volunteers with Various Genotypes: A Single-Center, Open-Label, Multiple-Dose Study

Clinical Drug Investigation ◽

10.1007/s40261-016-0380-4 ◽

2016 ◽

Vol 36 (5) ◽

pp. 369-376 ◽

Cited By ~ 2

Author(s):

Xia Chen ◽

Qian Zhao ◽

Ji Jiang ◽

Jian Liu ◽

Pei Hu

Keyword(s):

Multiple Dose ◽

Healthy Adult ◽

Single Center ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study

Download Full-text

Preclinical toxicology of a novel polymeric antitumour agent: HPMA copolymerdoxorubicin (PK1)

Human & Experimental Toxicology ◽

10.1177/096032719801700204 ◽

1998 ◽

Vol 17 (2) ◽

pp. 93-104 ◽

Cited By ~ 2

Author(s):

R Duncan ◽

J K Coatsworth ◽

S Burtles

Keyword(s):

Single Dose ◽

Multiple Dose ◽

Clinical Chemistry ◽

Testicular Atrophy ◽

Phase I Clinical Trials ◽

Polymer Backbone ◽

Single Dose Study ◽

Blood Samples ◽

Multiple Dose Study ◽

Dose Study

N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (PK1) is a novel polymeric anticancer agent containing doxorubicin (approximately 8 wt%) bound to the polymer backbone via a Gly-Phe-Leu-Gly peptidyl linker. The approximate LD50 of PK1 in MF1 mice after a single i.v. injection was 63 mg/kg (doxorubicin-equivalent). Single doses of PK1 were administered to MF1 mice at 22.5 or 45 mg/kg and blood samples taken on days 3, 7 and 14 for haematological examination and clinical chemistry. At day 14 all animals were sacrificed for necropsy. In a multiple dose study, PK1 was administered i.v. to MF1 mice or Wistar rats (20 animals per group) weekly for five consecutive weeks at doses of 12.0 or 22.5 mg/kg (mice) or 3 and 5 mg/kg (rats). After 31 days 10 animals from each group were sacrificed for necropsy and the remainder were sacrificed after 59 days. Blood samples were taken 3 days after administration of each dose and at the end of the experiment, and urine samples were collectedonthe day prior to sacrifice.Mortality inthe single dose mouse and multiple dose rat studies was low. In the multiple dose mouse study 4/10 animals were killed in extremis before the scheduled day 31 and all animals died before day 37. PK1 induced a reduction in WBC and platelets in rats and mice shortly after treatment and RBC at later times, and in the single dose study alanine and aspartate aminotransferase levels were elevated at higher doses. Liver damage was seen only in rat tissue during histological examination. Other histological changes induced by PK1 include thymic and testicular atrophy, bone marrow depletion gastrointestinal tract changes and in the multiple dose study an increase in nuclear size in the proximal tubules of the kidney (although no changes in urine were seen). Recovery from these effects was seen in rats at 59 days. A PK1 dose of 20 mg/m2 (doxorubicin equivalent) was recommended as a safe dose for the start of Phase I clinical trials.

Download Full-text

Safety, Tolerability, and Pharmacokinetics of PA-824 in Healthy Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00106-09 ◽

2009 ◽

Vol 53 (9) ◽

pp. 3720-3725 ◽

Cited By ~ 94

Author(s):

Ann M. Ginsberg ◽

Martino W. Laurenzi ◽

Doris J. Rouse ◽

Karl D. Whitney ◽

Melvin K. Spigelman

Keyword(s):

Mycobacterium Tuberculosis ◽

Single Dose ◽

Healthy Subjects ◽

Multiple Dose ◽

Pharmacokinetic Parameters ◽

Blood Levels ◽

Drug Resistant ◽

Single Dose Study ◽

Multiple Dose Study ◽

Dose Study

ABSTRACT PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.25 μg/ml for drug-sensitive strains and between 0.03 and 0.53 μg/ml for drug-resistant strains. In addition, it is active against nonreplicating anaerobic Mycobacterium tuberculosis. The safety, tolerability, and pharmacokinetics of PA-824 were evaluated in two escalating-dose clinical studies, one a single-dose study and the other a multiple-dose study (up to 7 days of daily dosing). In 58 healthy subjects dosed with PA-824 in these studies, the drug candidate was well tolerated, with no significant or serious adverse events. In both studies, following oral administration PA-824 reached maximal plasma levels in 4 to 5 h independently of the dose. Maximal blood levels averaged approximately 3 μg/ml (1,500-mg dose) in the single-dose study and 3.8 μg/ml (600-mg dose) in the multiple-dose study. Steady state was achieved after 5 to 6 days of daily dosing, with an accumulation ratio of approximately 2. The elimination half-life averaged 16 to 20 h. Overall, PA-824 was well tolerated following oral doses once daily for up to 7 days, and pharmacokinetic parameters were consistent with a once-a-day regimen. The results of these studies, combined with the demonstrated activity of PA-824 against drug-sensitive and multidrug-resistant Mycobacterium tuberculosis, support the investigation of this novel compound for the treatment of tuberculosis.

Download Full-text