PARALLEL DETERMINATION OF GUT PERMEABILITY IN MAN WITH M(R)-400, M(R)-1500, M(R)-4000 AND M(R)-10000 POLYETHYLENE-GLYCOL

Polyethylene glycol has been in use for a number of years for the asse ssment of gut permeability. The methods so far employed are usually li mited to polyethylene glycols in the low relative molecular mass range (up to M(r) 1300). We developed a method for the simultaneous determi nation of gut permeability to M(r) 400, M(r) 1500, M(r) 4000 and M(r) 10 000 polyethylene glycol, by applying a single oral dose of an appro priate mixture of these polyethylene glycols. After extraction from 24 h-urine, M(r) 1500, M(r) 4000 and M(r) 10 000 polyethylene glycol wer e quantified by size exclusion chromatography, while M(r) 400 polyethy lene glycol was determined by reversed phase chromatography. The detec tion limit of polyethylene glycol in the relative molecular mass range between M(r) 1500 and M(r) 10 000 was found to be 0.2 mg/l urine, and the detection limit of M(r) 400 polyethylene glycol 5 mg/l urine. Rec overy of the polyethylene glycols (N = 6) were 86.6% (CV: 4.8%) for M( r) 400, 94.1% (CV: 7.2%) for M(r) 1500, 97.1% (CV: 5.5%) for M(r) 4000 and 97.4% (CV: 5.6%) for M(r) 10 000. No significant difference was f ound between the excretion rates in 24 h-urine of M(r) 400 and M(r) 15 00 polyethylene glycols in patients with Crohn's disease (M(r) 400: 34 .4 +/- 5.5%; M(r) 1500: 5.22 +/- 2.27%; mean +/- SEM, N = 10) and heal thy controls (M(r) 400: 33.6 +/- 3.2%, M(r) 1500: 1.09 +/- 0.26%; N = 21). The excretion rate of M(r) 4000 polyethylene glycol was markedly higher in patients with Crohn's disease (0.462 +/- 0.177%) than in hea lthy controls (0.049 +/- 0.012%, p < 0.05). M(r) 10 000 polyethylene g lycol was detected in the urine of only one out of the 21 healthy cont rols, but in nine out of the ten patients with Crohn's disease (p < 0. 001). These results suggest a change not in number but rather in selec tivity in permeability of high M(r) molecules.