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

1 Introduction

Lactulose is a synthetic disaccharide composed of fructose and galactose. There are no enzymes that degrade lactulose into monosaccharides in the human gastrointestinal tract. In the human body, most of the lactulose reaches the lower gastrointestinal tract and converts to organic acids (lactic acid, acetic acid, etc.) by bacterial decomposition, thereby lowering the pH ^[1]. Due to acidification of the intestinal tract, the number of fully-grown lactic acid bacteria increases, whereas the number of bacteroides and Escherichia coli decreases ^[2,3]. In agreement, it was also reported that lactulose has prebiotic-like effects against inflammatory bowel disease ^[4]. By increasing the amount of H⁺ in the intestinal tract, the NH₃ would preferentially convert to nonabsorbable NH₄⁺, thus lowering the ammonia concentration in blood ^[5], for which can treat hepatic encephalopathy or related seizures ^[6]. It has also been shown that a laxative effect is induced in the lower gastrointestinal tract by osmotic regulation.

Due to toxic compounds that are accumulated in patients with chronic renal failure (CRF) ^[7], some treatments are able to assist with the excretion of unwanted wastes from bodies. In 1971, lactulose therapy was first applied to treat uremic toxins in patients with CRF ^[8]. Based on a published study conducted with healthy men, lactulose was poorly absorbed and could be found in urinary excretion relative to its oral amount by only 0.65% ^[9]. However, given that CRF is usually altered the pharmacokinetic profile of medicines, it is necessary to understand the plasma transition of lactulose in patients with impaired renal function and on dialysis.

For this study, our purpose was to investigate the pharmacokinetics of lactulose including the removal rate of dialysis by administering a single oral dose of lactulose (6.5 g) in hemodialysis patients.

2 Materials and methods
2.1 Drug information

The investigational drug was a jelly containing 6.5-g lactulose (Lagnos Jelly Divided Pack 16.05 g, Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Japan).

2.2 Study population and design

A total of six hemodialysis patients were proposed to enroll into the study. This study followed the Taiwan Law of Pharmaceutical Affairs, Good Clinical Practices, local regulatory requirements, and was according to the Revised Declaration of Helsinki ^[10]....