Phase I Study of ZD4522 (Rosuvastatin), a New HMG-CoA Reductase Inhibitor-Evaluation of tolerance and Pharmacokinetics in Healthy Adult Male Volunteers after Single and Repeated Oral Administration-
|
Accession number;05A0194380
|
| Title;Phase I Study of ZD4522 (Rosuvastatin), a New HMG-CoA Reductase Inhibitor-Evaluation of tolerance and Pharmacokinetics in Healthy Adult Male Volunteers after Single and Repeated Oral Administration- |
| Author;
SEKINO HISAKUNI
(Sekino Rinsho Yakuri Kurinikku)
ONISHI TATSUO
(Asutorazeneka)
|
Journal Title;Journal of Clinical Therapeutics & Medicines
|
Journal Code:Y0906A
|
ISSN:0910-8211
|
|
VOL.21;NO.2;PAGE.187-203(2005)
|
| Figure&Table&Reference;FIG.5, TBL.10, REF.8 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;A placebo-controlled, double-blind study was conducted in 24 Japanese healthy adult male volunteers to evaluate the tolerance, Pharmacokinetics and pharmacodynamic effects of rosuvastatin administered at single as well as 7 daily oral doses of 10, 20, and 40 mg. Seven of 18 subjects receiving rosuvastatin (38.9%) developed a total of 17 adverse events, while 4 of 6 subjects receiving placebo (66.7%) developed a total of 10 adverse events. Of these events, 6 reported in 2 subjects receiving rosuvastatin (constipation, nausea, vomiting [n = 2] and headache, and increased CK) and 3 reported 1 placebo recipient (weakness of both upper limbs, left elbow pain and increased total bilirubin) were potentially related to the trial treatment. All adverse events were mild and transient and none of them was so serious that required any specific treatment or discontinuation of the study. The severity or incidence of the adverse events was not dose-related. After single or repeated doses of rosuvastatin, the Cmax and AUC(0-.INF.) for rosuvastatin increased almost in proportionally with dose, whereas the tmax and t1/2 remained relatively constant, being 3.5-5 hours and 13.5-19.1 hours, respectively. Based on the blood concentration observed at 24 hours after each dose, steady-state pharmacokinetics of the drug was reached on almost the 3rd day of administration. The values of AUC (0-24) at steady state were similar to the AUC (0-.INF.) after single dose, and an accumulation ratio was 1.2-1.4. The Cmax and AUC (0-24) data obtained after single doses of rosuvastatin involved a great variation, in the all groups, and the coefficient of variation (CV) ranged from approximately 25% to 55%. (author abst.) |
|
|
|
Related Articles;
|
|
