| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Youn Choi, Hee Jin, Seok-Joon Jung, Jin Ah Kim, Un-Jib Ko, Young-Ju Noh, Yook-Hwan Bae, Kyun-Seop Lim, Hyeong-Seok |
| Description |
Author Affiliation: Youn Choi H ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Jin SJ ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Jung JA ( Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.); Kim UJ ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Ko YJ ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Noh YH ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Bae KS ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea); Lim HS ( Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Seoul, Republic of Korea) |
| Abstract |
BACKGROUND: CG100649, a novel selective cyclooxygenase-2 inhibitor that also inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk typical of other NSAIDs. Concurrent medications may influence the activities of the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized. OBJECTIVES: This study was designed to evaluate the influence of ketoconazole, a known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649. METHODS: This randomized, open-label, 2 × 2 crossover study was conducted in healthy Korean male volunteers. Each subject received the following 2 treatments in a randomly allocated sequence, separated by a washout period of 42 days: single oral dose of CG100649 6 mg, and concurrent dosing of CG100649 6 mg and ketoconazole 400 mg followed by ketoconazole 400 mg/d over 4 days. Blood samples for pharmacokinetic analysis were collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 240, 384, and 480 hours after dosing of CG100649 in each sequence. Tolerability assessments were performed throughout the study. RESULTS: Thirty subjects participated, and 26 subjects completed the study. Seventeen adverse events (AEs) were reported in 10 subjects, and all AEs were recovered without any sequelae. No serious AEs were reported. Six subjects receiving the single dose of CG100649 had 9 AEs, and 7 subjects receiving the combination of ketoconazole and CG100649 had 8 AEs. The Cmax of CG100649 with CG100649 only and with concurrent administration of CG100649 + ketoconazole were similar (10.7 and 11.0 ng/mL, respectively). The CG100649 AUClast with concurrent ketoconazole was 1.29-fold greater than that with CG100649 only (2074.0 and 2685.8 ng · h/mL) and demonstrated a statistically significant difference (P < 0.05). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or AEs between treatments. CONCLUSION: Although the AUC of CG100649 increased by 29% with the concurrent medication of ketoconazole, it is considered that concurrent administration of CG100649 with ketoconazole would not change the safety profile of CG100649. |
| File Format |
HTM / HTML |
| ISSN |
01492918 |
| Issue Number |
1 |
| Volume Number |
36 |
| e-ISSN |
1879114X |
| Journal |
Clinical Therapeutics |
| Language |
English |
| Publisher |
Elsevier |
| Publisher Date |
2014-01-01 |
| Publisher Place |
United States |
| Access Restriction |
One Nation One Subscription (ONOS) |
| Subject Keyword |
Discipline Pharmacology Carbonic Anhydrase Inhibitors Adverse Effects Pharmacokinetics Cyclooxygenase 2 Inhibitors Cytochrome P-450 Cyp3a Inhibitors Ketoconazole Administration, Oral Adult Administration & Dosage Cross-over Studies Drug Administration Schedule Drug Synergism Humans Male Middle Aged Young Adult Journal Article Randomized Controlled Trial Research Support, Non-u.s. Gov't |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Pharmacology Pharmacology (medical) |
