Pharmacokinetic drug-drug interaction study of ranolazine and metformin in subjects with type 2 diabetes mellitus
| Autor: | Julia, Zack, Jolene, Berg, Axel, Juan, Nicola, Pannacciulli, Martine, Allard, Mildred, Gottwald, Heather, Zhang, Yongwu, Shao, Ori, Ben-Yehuda, Phil, Jochelson |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Metabolic Clearance Rate Organic Cation Transporter 2 Cardiovascular Agents CHO Cells Comorbidity Middle Aged Metformin United States Angina Pectoris Cricetulus Diabetes Mellitus Type 2 Double-Blind Method Ranolazine Area Under Curve Chronic Disease Polypharmacy Animals Humans Hypoglycemic Agents Drug Interactions Female Aged |
| Zdroj: | Clinical pharmacology in drug development. 4(2) |
| ISSN: | 2160-7648 |
| Popis: | Ranolazine and metformin may be frequently co-administered in subjects with chronic angina and co-morbid type 2 diabetes mellitus (T2DM). The potential for a drug-drug interaction was explored in two phase 1 clinical studies in subjects with T2DM to evaluate the pharmacokinetics and safety of metformin 1000 mg BID when administered with ranolazine 1000 mg BID (Study 1, N = 28) or ranolazine 500 mg BID (Study 2, N = 25) as compared to metformin alone. Co-administration of ranolazine 1000 mg BID with metformin 1000 mg BID resulted in 1.53- and 1.79-fold increases in steady-state metformin Cmax and AUCtau , respectively; co-administration of ranolazine 500 mg BID with metformin 1000 mg BID resulted in 1.22- and 1.37-fold increases in steady-state metformin Cmax and AUCtau , respectively. Co-administration of ranolazine and metformin was well tolerated in these T2DM subjects, with no serious adverse events or drug-related adverse events leading to discontinuation. The most common adverse events were nausea, diarrhea, and dizziness. These findings are consistent with a dose-related interaction between ranolazine and metformin, and suggest that a dose adjustment of metformin may not be required with ranolazine 500 mg BID; whereas, the metformin dose should not exceed 1700 mg of total daily dose when using ranolazine 1000 mg BID. |
| Databáze: | OpenAIRE |
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