Assessment of the pharmacokinetics, removal rate of hemodialysis, and safety of lactulose in hemodialysis patients

Lactulose is often used to treat hepatic encephalopathy or constipation, and also exhibits benefits to chronic renal insufficiency due to reduce nitrogen-related products in serum. The present study investigated the pharmacokinetics of lactulose, its removal rate through dialysis, and safety by administering lactulose 6.5 g (Lagnos Jelly Divided Pack 16.05 g) orally to six hemodialysis patients who resided in Taiwan. As a result, the means of maximum plasma concentrations (C(max)) and Time to reach C(max) (Tmax) were 3090 ± 970 ng/mL and 6.5 ± 2.3 hours, respectively. The mean plasma concentration was 2220 ± 986 ng/mL after administration for 24 hours. Sequentially, the mean plasma concentration reduced to 307 ± 117 ng/mL after the application of 4-hour dialysis. Area under the plasma concentration-time curve from zero to 24 h post-dose (AUC(0–24h)) were 56,200 ± 21,300 ng h/mL and the AUC(0–28h) was 61,200 ± 23,300 ng h/mL. The rate of lactulose removal by dialysis was 83.6 ± 8.9%. In addition, the multiple doses of lactulose using a simulated model suggested that no plasma accumulation would be expected while coordinating with dialysis. Good tolerability was confirmed, while the mild adverse effect of diarrhea was observed in one case during the study period. No death or serious adverse effect was reported. Based on the present study, we demonstrated the pharmacokinetic transition with respect to plasma levels of lactulose in patients with impaired renal excretion treated with hemodialysis.