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There are a number of drugs that affect the clearance of repaglinide. The physician should take into account possible interactions. With In vitro,: Repaglinide is metabolized primarily influenced isoenzymes.

Clinical studies in durabolin 100 healthy volunteers have shown that the most important isoenzyme involved in the metabolism of repaglinide, a CYP2C8, a CYP3A4 playing a minor role, but its relative contribution It can be increased in cases when there is an isoenzyme inhibition CYP2C8. Consequently metabolism, and thus, repaglinide clearance may change under the influence of drugs that affect, inhibiting or inducing isoenzymes of cytochrome P-450.

Particular care should be taken while the use of repaglinide inhibitors isoenzymes CYP2C8 and of CYP3A4. Based on the data in vitro and in vivo repaglinide is actively absorbed by the liver (anion-transporting protein OATR1V1). OATR1V1 inhibitors (e.g., cyclosporin) can also increase the concentration of repaglinide in plasma. The following drugs may enhance and / or prolong the hypoglycemic action of repaglinide: gemfibrozil, trimethoprim, rifampin, clarithromycin, ketoconazole, itraconazole, cyclosporine, other hypoglycemic drugs, monoamine oxidase inhibitors, nonselective . beta-blockers, angiotensin-converting enzyme inhibitors, salicylates, non-steroidal anti-inflammatory drugs, octreotide, alcohol and anabolic steroids Studies on drug interactions in healthy volunteers showed that the simultaneous use of gemfibrozil  resulted in an increase in AUC values repaglinide 8.1 times the value C max – 2.4 times and an increase in t 1/2 of 1.3 to 3, 7:00, which could lead to a strengthening and extension hypoglycemic effect of repaglinide.Therefore, the simultaneous use of gemfibrozil and repaglinide is contraindicated due to a significant increase in repaglinide plasma concentrations.

Studies on drug interactions repaglinide with fenofibratewere not carried out. With the simultaneous use of trimethoprim, but this no significant effect was detected at concentration of glucose in the blood. However, this lack of pharmacodynamic effect was detected in sub-therapeutic doses of repaglinide. Since this combination of the safety profile has not been assessed in doses greater than 0.25 mg for repaglinide and 320 mg – for trimethoprim, care should be taken while the use of these drugs. If there is still a need for concomitant use of these dr

With simultaneous use of rifampicin and repaglinide dose adjustment may require repaglinide, which should be based on the results careful monitoring of blood glucose; monitoring should be performed at initiation of therapy with rifampicin (acute inhibition); after dosing (mixed impact – inhibition and induction); then when canceling rifampicin (induction only), and finally after about one week after withdrawal of rifampicin, rifampicin inducing action when no longer appears. The effect of ketoconazole , the prototype being potent inhibitors isoenzyme CYP3A4, repaglinide pharmacokinetics was studied in healthy volunteers. When assigning ketoconazole durabolin 100 (200 mg daily), with repaglinide simultaneously (in a dose of 4 mg once daily) was registered an increase in mean repaglinide systemic exposure (AUC and C max ) of 1.2 times, while the blood glucose concentration varied by less than 8%. Interaction withitraconazole (an inhibitor of isozyme CYP3A4) in a dose of 100 mg was also studied in healthy volunteers and have been shown to increase in AUC 1.4 fold. When this was not observed any significant effect on the glucose concentration in healthy volunteers.

In studies in healthy volunteers joint application of 250 mg of clarithromycin, which is due to the mechanism of action is a potent inhibitor of isozyme CYP3A4, showed a slight increase in repaglinide systemic exposure (AUC increased 1.4 times, a C max – 1.7 times), the average value of serum insulin AUC increased 1.5 times, and the C max – 1.6 times.The exact mechanism of this interaction is unclear. Tacrolimus (100 mg), isozyme CYP3A4 inhibitor and a potent inhibitor OATR1V1, increased C max repaglinide (0.25 mg dose) 1.8 times and 2.5 times the AUC in healthy volunteers in the study. Since drug interactions are not evaluated at doses higher than 0.25 mg for repaglinide, it is recommended to avoid concomitant administration of cyclosporine and repaglinide. If, however, there was a need for simultaneous prescription of these drugs, it is necessary to closely monitor the concentration of glucose in the blood, as well as the clinical observation of the patient (see. Section “Special Instructions”). The study of interactions in healthy volunteers showed that the co-administrat. Concomitant use of cimetidine, nifedipine, estrogen, or simvastatin (all these drugs are substrates isoenzyme CYP3A4) with repaglinide had no significant effect on the pharmacokinetic parameters of repaglinide. repaglinide no clinically significant effect on the pharmacokinetics of digoxin, theophylline or warfarin at steady state in healthy volunteers applied. Thus, there is no need for correction of doses of these drugs when used together with repaglinide. The following substances may reduce the hypoglycemic effect of repaglinide: oral contraceptives, rifampicin, barbiturates, carbamazepine, derivatives thiazide, glucocorticosteroids, danazol, thyroid hormones and sympathomimetics. Combined use peroralnyh contraceptives (ethinyl estradiol / levonorgestrel) does not lead to clinically significant change in the overall bioavailability of repaglinide, repaglinide concentration at the maximum reached before. Repaglinide durabolin 100 clinically not significantly affect the bioavailability of levonorgestrel, but it can not be ruled out its effect on the bioavailability of ethinyl estradiol. In this regard, during the period of application or withdrawal of these drugs, patients who are already receiving repaglinide should be monitored carefully for early detection of disorders of glycemic control. buy anabolic steroids online bruce lee’s workout anabolic steroids online uk