RESUMO
This open-label, parallel-group study evaluated the effect of mild and moderate hepatic impairment on the pharmacokinetics of a single dose of luseogliflozin in Japanese subjects. Thirteen subjects with hepatic impairment (mild, n = 8; moderate, n = 5) and 6 healthy subjects received a single 5-mg dose of luseogliflozin. Serial blood sampling over 72 hours and 24-hour urine collection were done for pharmacokinetic analysis of luseogliflozin and its metabolites and to measure pharmacokinetic and pharmacodynamic parameters, respectively. Demographic characteristics were similar at baseline for both groups. Geometric mean ratios of maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve from time zero to infinity (AUCinf [90%CI]) of unchanged luseogliflozin were 1.02 (0.790-1.32) and 0.774 (0.580-1.03), respectively, on comparing patients with hepatic impairment with healthy subjects, and 0.939 (0.752-1.17) and 1.00 (0.780-1.28), respectively, in subjects with mild and moderate hepatic impairment. Although mean plasma concentrations of metabolites were slightly higher in patients with hepatic impairment versus healthy subjects, their time-course plasma concentrations were very low compared with those of unchanged luseogliflozin. Single-dose luseogliflozin 5 mg was well tolerated by study participants, indicating luseogliflozin dose adjustment is not necessary in patients with mild and moderate hepatic impairment.
Assuntos
Hipoglicemiantes/farmacocinética , Hepatopatias/metabolismo , Sorbitol/análogos & derivados , Adulto , Idoso , Área Sob a Curva , Feminino , Glucose/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hepatopatias/sangue , Hepatopatias/urina , Masculino , Pessoa de Meia-Idade , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose , Sorbitol/administração & dosagem , Sorbitol/farmacocinéticaRESUMO
A prospective, randomised, double-blind, parallel-group, dose-response trial was conducted to investigate the antiproteinuric effect of candesartan cilexetil, the angiotensin II type 1 receptor blocker, in patients with chronic glomerulonephritis. Patients (n=280) were treated for 12 weeks with candesartan cilexetil 2, 4, or 8 mg given orally once-daily (o.d.). The improvement in urinary protein excretion observed at the end of the treatment period was 15.9% in the 2 mg group, 25.6% in the 4 mg group, and 34.6% in the 8 mg group, respectively, showing a clear dose-response (2 mg <4 mg <8 mg; p=0.003). The mean reduction in urinary protein excretion was 11.3% in the 2 mg group, 26.3% in the 4 mg group, and 26.0% in the 8 mg group, showing a dose-response pattern, in that the effect of 4 mg and 8 mg was greater than that of 2 mg (2 mg <4 mg asymptotically equal to 8 mg; p=0.010). As the observed reduction in urinary protein excretion failed to correlate with changes in mean blood pressure, it could not be attributed to the antihypertensive effect of the study drug alone. This suggests that candesartan cilexetil, 4 8 mg o.d., has antiproteinuric effects in patients with chronic glomerulonephritis.