Each nitrofurantoin monohydrate/macrocrystals capsule contains two forms of nitrofurantoin. Twenty-five percent is macrocrystalline nitrofurantoin, which has slower dissolution and absorption than nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend which, upon exposure to gastric and intestinal fluids, forms a gel matrix that releases nitrofurantoin over time. Based on urinary pharmacokinetic data, the extent and rate of urinary excretion of nitrofurantoin from the 100 mg nitrofurantoin monohydrate/macrocrystalscapsule are similar to those of the 50 mg or 100 mg nitrofurantoin macrocrystals capsule. Approximately 20 to 25% of a single dose of nitrofurantoin is recovered from the urine unchanged over 24 hours.
Plasma nitrofurantoin concentrations after a single oral dose of the 100 mg nitrofurantoin monohydrate/macrocrystals capsule are low, with peak levels usually less than 1 mcg/mL. Nitrofurantoin is highly soluble in urine, to which it may impart a brown color. When nitrofurantoin monohydrate/macrocrystals is administered with food, the bioavailability of nitrofurantoin is increased by approximately 40%.
Microbiology: Nitrofurantoin is bactericidal in urine at therapeutic doses. The mechanism of the antimicrobial action of nitrofurantoin is unusual among antibacterials. Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates which inactivate or alter bacterial ribosomal proteins and other macromolecules. As a result of such inactivations, the vital biochemical processes of protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis are inhibited. The broad-based nature of this mode of action may explain the lack of acquired bacterial resistance to nitrofurantoin, as the necessary multiple and simultaneous mutations of the target macromolecules would likely be lethal to the bacteria. Development of resistance to nitrofurantoin has not been a significant problem since its introduction in 1953. Cross-resistance with antibiotics and sulfonamides has not been observed, and transferable resistance is, at most, a very rare phenomenon.
Nitrofurantoin, in the form of nitrofurantoin monohydrate/macrocrystals, has been shown to be active against most strains of the following bacteria both in vitro and in clinical infections: (See INDICATIONS AND USAGE).
Nitrofurantoin also demonstrates in vitro activity against the following microorganisms, although the clinical significance of these data with respect to treatment with nitrofu-rantoin monohydrate/macrocrystals is unknown:
(including Staphylococcus epidermidis)
Group D streptococci
Viridans group streptococci
Nitrofurantoin is not active against most strains of Proteus species or Serratia species. It has no activity against Pseudomonas species.
Antagonism has been demonstrated in vitro between nitrofurantoin and quinolone antimicrobials. The clinical significance of this finding is unknown.
Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC’s). These MIC’s provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC’s should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of nitrofurantoin powder. The MIC values should be interpreted according to the following criteria:
| MIC (mcg/mL) || Interpretation |
| ≤ 32 || Susceptible (S) |
| 64 || Intermediate (I) |
| ≥ 128 || Resistant (R) |
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the urine reaches the concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard nitrofurantoin powder should provide the following MIC values:
| Microorganism || MIC (mcg/mL) |
| E. coli ATCC 25922 || 4 to 16 |
| S. aureus ATCC 29213 || 8 to 32 |
| E. faecalis ATCC 29212 || 4 to 16 |
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 300 mcg nitrofurantoin to test the susceptibility of microorganisms to nitrofurantoin.
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 300 mcg nitrofurantoin disk should be interpreted according to the following criteria:
| Zone Diameter (mm) || Interpretation |
| ≥ 17 || Susceptible (S) |
| 15 to 16 || Intermediate (I) |
| ≤ 14 || Resistant (R) |
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for nitrofurantoin.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 300 mcg nitrofurantoin disk should provide the following zone diameters in these laboratory test quality control strains:
| Microorganism || Zone Diameter (mm) |
| E. coli ATCC 25922 || 20 to 25 |
| S. aureus ATCC 25923 || 18 to 22 |