Pharmacokinetic Profile of Fosfomycin Trometamol

Abstract

The pharmacokinetics of fosfomycin trometamol has been assessed in 12 healthy volunteers given oral doses of 2, 3, and 4 g of fosfomycin and 3 g intravenously of fosfomycin as fosfomycin sodium, all in the fasting state. The assay was microbiological (Proteus mirabilis ATCC 21100). There was a gradual rise in both peak serum concentrations and total area under the curve by rising oral doses, from 16.0 mg/l and 106.7 mg x h/1, after 2 g to 30.9 mg/l and 189.7 mg x h/1 after 4 g respectively. The serum half-life was 4 h after the oral doses and 2.1 h after the intravenous dose. After the oral doses, the amounts excreted in urine in the active form ranged from 36 to 40% compared to 93% after the intravenous dose. The bioavailability was slightly below 40%. Concentrations in urine covers the usual urinary tract pathogens after oral doses of 2, 3, and 4 g.

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

“…40% [11]. Administration of fosfomycin tromethamine with food may reduce the degree of drug absorption [12].…”

An infectious disease and pharmacokinetic perspective on oral antibiotic treatment of uncomplicated urinary tract infections due to multidrug-resistant Gram-negative uropathogens: the importance of urinary antibiotic concentrations and urinary pH

“…In contrast, "high resistance potential" antibiotics often predispose to resistance even with limited use, e.g., ciprofloxacin [12,13,15,25] ( Table 4). Clearly, the three most useful, "low resistance potential" oral antibiotics ideal for the treatment of MDR GNB uropathogens are nitrofurantoin, doxycycline, and fosfomycin [15,25,[28][29][30][31][32][33][34][35][36]. These "low resistance potential" antibiotics are well tolerated and, properly used, have a good safety profile [15].…”

Fosfomycin and Its Application in the Treatment of Multidrug-Resistant Enterobacteriaceae Infections

“…44 In spite of 40 years of evolution of methods to determine fosfomycin concentrations, there has been almost no progress in lowering the limit of sensitivity of the assays, which is approximately 1 mg/L by gas chromatography 43,49,50 or by capillary gas chromatography, 51,52 while by microbiological methods, it is reported to be 0.7-1.5 mg/L when mentioned. 47,48,53,54 …”

“…44,48,53 Fosfomycin trometamine is thought to dissociate into fosfomycin acid and trometamine at the absorption stage, 55 and then fosfomycin absorption is mediated via the intestinal phosphate transport system. 56 After a single dose of fosfomycin 3 g, the bioavailability ranges from 34% to 58%, 31,44,53,55,57 with a peak plasma concentration ranging from 12 to 32 mg/L and a delay of 2-4 hours. Because fosfomycin is not metabolized and the nonrenal clearance is negligible, 30 the main route of excretion is in the urine.…”

“…Elimination is prolonged, with mean concentrations above 128 mg/L for more than 24 hours. 52,53 The concentration achieved in urine is the main criterion for the break points chosen by the Clinical and Laboratory Standards Institute. 58 When fosfomycin is taken with food, the peak urinary concentration is lower and appears later.…”