Effect of pitavastatin in different SLCO1B1 backgrounds on repaglinide pharmacokinetics and pharmacodynamics in healthy Chinese males
Effects of SLCO1B1 Polymorphism and Pitavastatin on the Pharmacokinetics of Repaglinide in Chinese Healthy Volunteers
Third Xiangya Hospital, Central South University
12 participants
Mar 5, 2009
Interventional
Conditions
Summary
1. SLCO1B1 genetic polymorphism had no effect on the pharmacokinetic profile of repaglinide. After repaglinide administration, higher concentrations were seen in the SLCO1B1*15 carriers. Two common SLCO1B1 single nucleotide polymorphisms (SNPs) c.A388G and c.T521C form four functionally distinct SLCO1B1 haplotypes: *1a (c.388A/c.521T), *1b (c.388G/c.521T), *5 (c.388A/c.521C), and *15 (c.388G/c.521C). 2. Pitavastatin can increase plasma concentrations of repaglinide independent of SLCO1B1 genetic polymorphism, but has no effect on pharmacodynamics of repaglinide in healthy volunteers.
Eligibility
Inclusion Criteria6
- Subjects must be able to read and understand the contents of informed consent,and signed informed consent;
- Age 18-55 years old, male, no more than 10 years in age difference with the same batch (including the boundary values);
- Body weight > 50kg, the subjects body mass index (BMI) between 19-25kg/m2 (BMI = weight (kg) / height 2 (m2)), including the boundary values, the same batch weight difference should not be great;
- No history of alcohol abuse or drug abuse, non-smokers;
- They are ascertained to be healthy by physical examination such as blood pressure, heart rate, ECG, respiratory status, liver and kidney function and so on;
- Subjects can be able to make good communication with researchers and complete research in accordance with the provisions of study.
Exclusion Criteria14
- It is known that there are allergies for active pharmaceutical ingredients or excipients;
- Specific allergic history (asthma, urticaria, eczema, dermatitis), arrhythmia, bradycardia, hypotension, coronary heart disease, bronchial and cardiovascular diseases, diabetes, hyperthyroidism, Parkinson's disease, epilepsy , tremor, paralysis and any other diseases or physiological conditions interfering test results;
- Subjects are receiving or have been received gastrointestinal problems, seizures, gastrointestinal ulcers, urinary tract infarction, mechanical intestinal obstruction, ureteral spasm, biliary tract disease and other treatment of depressive disorders or liver disease;
- It is known that the factors can affect the venous blood of severe bleeding;
- Some gastrointestinal tract diseases can affect drug absorption or metabolism;
- Subjects have the history of drug abuse or positive urine drug test results within the past five years;
- The combined use of drugs that affect glucose metabolism, such as corticosteroids and so on;
- It is known to have used drugs that damage an organ within three months;
- It is known to have used other drugs that may affect the metabolism of hypoglycemic drugs within 14 days before the test (such as monoamine oxidase inhibitors, non-selective ß-blockers, ACEI, non-steroidal anti-inflammatory drugs, salicylates, octreotide , alcohol, anabolic growth hormone, oral contraceptives, thiazide drugs, corticosteroids, danazol, thyroid hormones, sympathomimetics, ketoconazole, itraconazole, erythromycin, fluconazole, and other azole anti-fungal, rifampicin, phenytoin, trimethoprim, cyclosporine, macrolide antibiotics erythromycin and clarithromycin, cimetidine, indomethacin,etc);
- A serious loss of blood or donating blood or plasma (300mL) within 30 days before the test;
- Primary disease in vital organs;
- Regular smokers or drinkers, that drinking more than 28 units of alcohol per week (1 unit: 285ml beer or 1 glass of wine or 25ml spirits) or weekly smoking over two or more cigarette;
- Often using sedatives, sleeping pills, tranquilizers or other addictive drugs;
- The researchers believe that some subjects should not be included.
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Interventions
Arm 1 4 mg pitavastatin once daily for 5 days, On day 5, 1 h after the last dose of pitavastatin administration, 4 mg of repaglinide was orally administrated. Arm 2 placebo, identical to pitavastatin only without the active ingredient once daily for 5 days,On day 5, 1 h after the last dose of placebo administration, 4 mg of repaglinide was orally administrated.
Locations(1)
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ACTRN12611001254987