Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis

Abstract

Methods:The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two-period crossover. Three female and two male patients (age range: 35-45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/ 100 mL. An unabsorbable radioactive marker ( 99mTc-labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema.Results : Budesonide plasma levels were measurable for up to 4-6 h. C, , , was 2.5 nmol/L (range: 0.9-4.5 nmol/L) and was attained in 1.5 h (range 1-3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation. Conclusion: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.

Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system

“…Also, the rate and extent of spreading was more variable with the latter formulations. The rapid evaporation of water from topical formulations influences the spreadability and results in an uneven topical dose within the treated area (Nyman-Pantelidis et al, 1994). The formulations also must be spread quickly and at multiple sites to ensure correct dosage.…”

Budesonide: Teaching an Old Dog New Tricks for Inflammatory Bowel Disease Treatment

“…Together with controlled-ileal-release capsules and pHmodified release capsules, a budesonide prodrug (budesonide-beta-D-glucuronide) [11] has been tested to allow a homogeneous release of the drug along the entire colon. Furthermore, budesonide enema and foam seem to be able to reach splenic flexure and sigmoid colon after rectal application [12,33]. Food had little influence over systemic availability, with following peak plasma concentrations of budesonide administered in controlled ileal release capsules being achieved at the same dose regardless of prandial status in patients with CD [14].…”

Budesonide for ulcerative colitis

“…The first study (21) showed that budesonide does not accumulate in the human body after 4 weeks of treatment; also, mean plasma cortisol values did not change during this period of time. The second study (16) showed that a low viscosity formulation of budesonide had an improved capacity to reach the more proximal parts of the colon, reaching the splenic flexure in 15 minutes. In the third study (22), a dose of 2 mg/day showed the same efficacy as the 4 mg/day dosage, but with less plasma cortisol suppression.…”

“…This explains the mere 10% of oral bio-availability and the low systemic action of budesonide. When administered as an enema to humans, budesonide reaches the splenic flexure (16). Its bioavailability then averages 15% in patients with UC.…”

“…In table I we summarized a compilation of four studies in which different pharmacokinetic aspects of budesonide in UC patients were evaluated (16,(21)(22)(23). The first study (21) showed that budesonide does not accumulate in the human body after 4 weeks of treatment; also, mean plasma cortisol values did not change during this period of time.…”