Pharmacokinetics

Following single or repeated intranasal applications of 0.2 gram of Bactroban Nasal t.i.d. for 3 days to five healthy adult male subjects, no evidence of systemic absorption of mupirocin was demonstrated. The dosage regimen used in this study was for pharmacokinetic characterization only. (See DOSAGE AND ADMINISTRATION for proper clinical dosing information.)

In this study, the concentrations of mupirocin in urine and of monic acid in urine and serum were below the limit of determination of the assay for up to 72 hours after the applications. The lowest levels of determination of the assay used were 50 ng/mL of mupirocin in urine, 75 ng/mL of monic acid in urine, and 10 ng/mL of monic acid in serum. Based on the detectable limit of the urine assay for monic acid, one can extrapolate that a mean of 3.3% (range: 1.2-5.1%) of the applied dose could be systemically absorbed from the nasal mucosa of adults .

Data from a report of a pharmacokinetic study in neonates and premature infants indicate that, unlike in adults, significant systemic absorption occurred following intranasal administration of Bactroban Nasal in this population. At this time, the pharmacokinetic properties of mupirocin following intranasal application of Bactroban Nasal have not been adequately characterized in neonates or other children less than 12 years of age, and in addition, the safety of the product in children less than 12 years of age has not been established.

The effect of the concurrent application of intranasal mupirocin calcium ointment, 2% with other intranasal products has not been studied. (See PRECAUTIONS , Drug Interactions . )

Following intravenous or oral administration, mupirocin is rapidly metabolized. The principal metabolite, monic acid, demonstrates no antibacterial activity. In a study conducted in seven healthy adult male subjects, the elimination half-life after intravenous administration of mupirocin was 20 to 40 minutes for mupirocin and 30 to 80 minutes for monic acid. Monic acid is predominantly eliminated by renal excretion. The pharmacokinetics of mupirocin has not been studied in individuals with renal insufficiency.

Microbiology

Mupirocin is an antibacterial agent produced by fermentation using the organism Pseudomonas fluorescens. Mupirocin inhibits bacterial protein synthesis by reversibly and specifically binding to bacterial isoleucyl transfer-RNA synthetase. Due to this mode of action, mupirocin demonstrates no in vitro cross-resistance with other classes of antimicrobial agents.

When mupirocin resistance does occur, it appears to result from the production of a modified isoleucyl-tRNA synthetase. High-level plasmid-mediated resistance (MIC >1024 mcg/mL) has been reported in some strains of S. aureus and coagulase-negative staphylococci.

Mupirocin is bactericidal at concentrations achieved topically by intranasal administration. However, the minimum bactericidal concentration (MBC) against relevant intranasal pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC). In addition, mupirocin is highly protein bound (>97%), and the effect of nasal secretions on the MIC's of intranasally applied mupirocin has not been determined.

Mupirocin has been shown to be active against most strains of methicillin-resistant S. aureus , both in vitro and in clinical studies of the eradication of nasal colonization. Bactroban Nasal only has established clinical utility in nasal eradication as part of a comprehensive program to curtail institutional outbreaks of infections with methicillin-resistant S. aureus . (See INDICATIONS AND USAGE.)

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