Trometamol-fosfomycin (Monuril) bioavailability and food-drug interaction

Abstract

A new water-soluble monobasic salt of fosfomycin with trometamol has recently been developed for oral administration. The objective of this study was to evaluate the pharmacokinetics of trometamol-fosfomycin (Monuril) in serum and in urine in 10 healthy volunteers after oral administration of one single dose (50 mg/kg). In the same volunteers the concentrations of fosfomycin were measured before and after food absorption, in serum and urine samples taken at t = 0, 2, 4, 6, 8 and 24 h after the dose (plus 0.5 and 1 h for serum samples). The measurement of fosfomycin levels was carried out by means of a microbiological procedure using Proteus mirabilis ATCC 21100 as test organism. The results indicated at 2 or 4 h serum peak levels ranging from 9 to 28 micrograms/ml, with mean values of about 17-21 micrograms/ml. The urine concentrations reached 2,000-2,500 micrograms/ml at 2 h, with high levels maintained till the 8th hour (1,200-2,750 micrograms/ml) and persistence of noticeable concentrations at 24 h (100-700 micrograms/ml). The influence of food absorption, even variable, decreased significantly the rate of absorption, with lower serum and urine levels, as measured in the same volunteers. Taking into account this factor influencing the bioavailability and the distribution of the drug, the results of the study confirm that a high proportion of the oral dose of trometamine salt of fosfomycin is absorbed; the extremely high urinary recovery of the drug even after food administration could certainly allow short-course therapy or even single-dose therapy in the treatment of uncomplicated urinary tract infection.