Effect of pharmacokinetic differences between men and women on pharmacodynamic target attainment of levofloxacin against streptococcus pneumoniae

ABSTRACT

A recently published study reported significantly slower systemic clearance, smaller steady-state volume of distribution, and greater Area Under the Curve [AUC] for levofloxacin in women compared to men [p<0.01]. Since the AUC[o-24]/MIC ratio predicts clinical and microbiological outcomes for fluoroquinolones, sex-related differences in levofloxacin pharmacokinetics may result in pharmacodynamic differences between men and women. To evaluate the pharmacodynamic [AUC[0-24]/MIC] of levofloxacin 500 mg and 750 mg against Streptococcus pneumoniae in men and women. Sex specific pharmacokinetic data were obtained from the previously mentioned study; likewise sex specific MIC data were obtained from the SENTRY Antimicrobial Surveillance Program [2004-2005], Monte Carlo simulations [10,000 subjects] were performed to calculate the probability of target attainment [PTA] as well as the cumulative fractions of response [CFR] for levofloxacin pharmacodynamic target of free AUC[0-24]/MIC >/= 33.7 for men and women. MIC[50] and MIC[90] for S. pneumoniae isolates were 1 and 1 microg/ml. 77.5% of all S. pneumoniae isolates have MIC value of 1 microg/ml. For the 500 mg levofloxacin dose, the PTA remained at acceptable range in women [85%] up to MIC 1 microg/ml, but declined very sharply in men [27%] at the same MIC; whereas the PTA approaching 100% in both men and women at MIC 1 microg/ml for the 750mg dose. At the mean time, while the CFR was 45.4% greater in women than men [41.7% for men, 87.1% for women] for 500 mg dose; it was only 2.3% greater in women [96.2% for men, 98.5% for women] for 750 mg dose. Sex-related differences in Levofloxacin pharmacokinetics result in substantially greater pharmacodynamic target attainment against S. pneumoniae in women than in men at the 500 mg dose, but not at the 750 mg dose. This finding suggests that levofloxacin 750 mg should be used to treat S. pneumoniae infections, especially in men