PI3K AKT Signaling Pathways no clinically significant changes in laboratory tests vital

90% confidence intervals were wide, indicating low precision for this comparison. The variability associated with GSK2248761 exposure Ergosterol was unexpectedly high due in part to 1 subject in group C whose exposure was approximately 2 to 3 fold higher compared with the median values for AUC and Cmax . Seventy six AEs were reported, most occurring before exposure to GSK2248761 . The most common AE was headache . The majority of AEs were mild , and there were no SAEs or deaths in the study. Three subjects discontinued because of AEs before exposure to GSK2248761 . There were no treatment related trends in blood chemistry, hematology, urinalysis, vital signs, or ECG findings. Although GSK2248761 could affect thyroid function, most thyroid function variables remained within normal limits, and no subjects experienced clinically significant abnormal values for any thyroid function parameter.
Raltegravir Coadministration of GSK2248761 200 mg QD and raltegravir 400 mg twice daily did not result in clinically significant PK interactions . A decrease in plasma raltegravir AUC PI3K AKT Signaling Pathways and Cmax of 18% and no change in Cτ were observed when RAL 400 mg BID was coadministered with GSK2248761 200 mg QD . Coadministration of RAL with GSK2248761 resulted in mean reases in plasma GSK2248761 AUC, Cmax, and Cτ of 15%, 16%, and 13%, respectively .The most frequently reported AE was nausea, occurring in 3 subjects receiving GSK2248761 alone . All AEs were mild. There were no SAEs or deaths reported, and no subjects discontinued the study due to an AE.
In addition, there were no clinically significant changes in electron microscopy vital signs or ECG findings, and no clinical laboratory values were reported during the study as AEs. CYP450 probes and boosted protease inhibitors Coadministration of metabolic probes with repeat doses of GSK2248761 100 mg resulted in reases in midazolam and dextromethorphan AUC of 54% and 83%, respectively. No changes were observed in plasma flurbiprofen AUC or in the 4 OH flurbiprofen AUC to flurbiprofen AUC ratio . When darunavir/ritonavir 600/100 mg BID was administered with GSK2248761 100 mg QD, there were no effects on DRV pharmacokinetics or on plasma RTV exposure . However, coadministration of lopinavir/ritonavir 400/100 mg BID with GSK2248761 100 mg QD was associated with decreases in plasma LPV AUC, Cmax, and Cτ , while plasma RTV AUC, Cmax, and Cτ were decreased by 19%, 21%, and 42%, respectively.
Coadministration of single and repeat doses of DRV/RTV or LPV/RTV with GSK2248761 reased plasma GSK2248761 exposures compared with GSK2248761 administered alone . In general, the reases in plasma GSK2248761 exposure were less than 2 fold, and GSK2248761 exposure reased more with single dose coadministration of LPV/RTV or DRV/RTV than with coadministration of repeat doses of LPV/RTV or DRV/RTV.AEs, 1 of which was possibly related to the study drug . There were no clinically significant changes in laboratory tests, vital signs, or ECG parameters. Drug Interactions With Supportive Medications Statins Mean plasma concentrations of select statins and statin metabolites when statins were administered alone or with GSK2248761 are presented in Figure 4. Coadministration of GSK2248761 200 mg QD with a single dose of atorvastatin 20 mg or rosuvastatin 10 mg reased AUC .