Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients.
A glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose-lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open-label, multiple-dose, 3-period, single-sequence crossover design: on days -1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose-lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability.
Roche Innovation Center of New York, New York, NY, USA.
S
S
Zhai
Roche Innovation Center of New York, New York, NY, USA.
A
A
Georgy
Roche Innovation Center of New York, New York, NY, USA.
Z
Z
Liang
Roche Innovation Center of New York, New York, NY, USA.
J
J
Zhi
D000328:Adult; D000368:Aged; D044482:Benzeneacetamides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D023381:Endpoint Determination; D020536:Enzyme Activators / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005941:Glucokinase / Q000187:drug effects / Q000378:metabolism*; D005905:Glyburide / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use
D044482:Benzeneacetamides; D001786:Blood Glucose; D020536:Enzyme Activators; D005941:Glucokinase; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000068900:Sitagliptin Phosphate; C553963:piragliatin
glucokinase activator; glyburide; pharmacodynamics; piragliatin