Discussion
diarrhea, Nephrotoxicity, hyperuricemia, gout, dry mouth, oral ulcer
HEPATOCELLULAR INJURY, HYPERURICEMIA, HYPERTRIGLYCERIDEMIA, GOUT, DRY MOUTH, ORAL ULCER
The present study was conducted based on a former phase I/IIa trial of HP501In the present study, we found that patient with hyperuricemia was well tolerated at a daily dose of 30–120 mg of HP501. No SAEs were reported in either of the cohorts. The most common AEs reported in this study were gout flare, diarrhea, elevated ALT, hypertriglyceridemia, dry mouth and oral ulcer. The incidences of AEs among the 5 active cohorts were not significantly different.Hepatocellular injury is one of the most common treatment-related AEs associated with uricosuric drugsDry mouth was the most common AE of HP501, as observed in the study conducted by Wang et al.Nephrotoxicity is regarded as a potential risk factor for URAT1 inhibitorsExcept for 14 cases of gout flares, all other reported AEs in the five cohorts were mild. Our data showed that 120 mg did not reach the minimum intolerable dose of HP501. The safety of HP501 demonstrated in this study supports the use of 90 or 120 mg of HP501 in subsequent clinical trials.Our pharmacokinetic results showed that plasma exposure (AUC and COur pharmacodynamic results did not correspond with the pharmacokinetic results. The curves of serum UA change showed that UA lowering effect of HP501 was increased with an increase in the administration dose from 30 to 90 mg. However, the curve of the 120 mg cohort almost coincided with that of the 90 mg cohort, indicating that the serum UA-lowering effect was similar between the 90 and 120 mg cohorts. The dose-proportionality analysis found that values of β of ΔCThe present study had several limitations. First, the total treatment duration was short. Further studies are required to evaluate the long-term activity and safety of HP501. Second, it has been reported that the prevalence of hyperuricemia is about 4.9% in Chinese women, which is slightly less prevalent than that in Chinese men (4.9% vs. 7.9%)