Rifaximin systemic absorption in patients with ulcerative colitis

Ulcerative colitis is a chronic in ̄ammatory disease of the large intestine, characterised by alternate phases of activity and remission. Its aetiology is unknown, but circumstantial evidence incriminates luminal bacteria and their products in its pathogenesis [1, 2]. Rifaximin (INN) is a rifamycin derivative and its antimicrobial spectrum includes aerobic and anaerobic Gram-positive and -negative bacteria [3, 4]. After oral administration it undergoes virtually no systemic absorption [5, 6] and in a recent pilot study, it was shown to be useful in patients with steroid-refractory severe ulcerative colitis [7]. Rifaximin pharmacokinetics have only been studied in healthy volunteers [5], and we have therefore investigated the plasma concentrations and urinary excretion in patients with active ulcerative colitis receiving a single oral dose of the drug. Twelve patients, 11 men and 1 woman aged from 20 to 70 years (median 41), with mild to moderate active ulcerative colitis were enrolled. Clinical disease and endoscopic activity was de®ned according to Truelove and Witts [8] and Baron et al. [9]. The demographic and clinical characteristics of the patients are shown in Table 1. Routine haematology and clinical chemistry tests were performed before and after the end of the study. The study was approved by the Local Ethics Committee and each patient gave informed consent. Rifaximin was administered as a single oral dose of 400 mg (two 200-mg tablets). Each patient fasted 8 h prior to administration of the drug and fasting was maintained for 2 h after dosing. Patients consumed a standard hospital meal 5 h after ingestion of the drug. All patients were under treatment with 20±40 mg per day of methylprednisolone i.v. and oral salicylates (2.0±2.4 g per day). Blood was sampled before and 1, 4, 8 and 24 h after drug administration and urine was collected at 0±4 h, 4±8 h and 8±24 h. Urine and plasma samples were stored at )20 °C and assayed by Larime S.A., Lagord (France), using high-performance liquid chromatography with electrochemical detection [5]. The limit of quantitation was 2 ng áml. In most plasma samples, rifaximin concentrations were below the detection limit (Table 2). Rifaximin was detected in only a few patients during the ®rst 8 h after administration. Table 2 shows the 24 h urinary excretion of rifaximin. Only minor amounts of rifaximin were detected in urine. No signi®cant statistical correlation was found between disease activity and plasma and urinary rifaximin. No adverse reactions were encountered and laboratory test values remained within the normal ranges. After a single oral dose of 400 mg of rifaximin in patients with mild or moderate ulcerative colitis, the mean total amount excreted in 24 h (36.6  22.2 lg) was similar to that found previously in 18 healthy male volunteers aged 18±40, median 22, years (27.9  21.3 lg) with mean [5]. Rifaximin was detected in plasma only in seven patients, and the total recovered in the urine was 0.009% of the dose, with a maximum of 0.021% (in healthy volunteers the corresponding values were 0.007% and 0.020%, respectively). These data suggest the virtual absence of absorption of this drug, which implies negligible passage into the general circulation. UnfortuEur J Clin Pharmacol (1998) 54: 91±93 Ó Springer-Verlag 1998