Ciprofloxacin

Additional information

Pharmacokinetics and dosing

Studies on sex differences in ciprofloxacin pharmacokinetics show conflicting results. In a Dutch prospective observational cohort study ciprofloxacin pharmacokinetics was studied in critically ill patients in intensive care (24 men, 8 women). Following intravenous administration of 400 mg ciprofloxacin, exposure was higher in women. The difference in AUC between men and women was not due to variation in body weight or differences in bioavailability and thus a lower clearance in women was suggested [2]. Similar conclusions were drawn in a study in healthy volunteers (8 men, 7 women) where women were found to have increased exposure and slower clearance [3]. Sex differences in ciprofloxacin pharmacokinetics were also investigated in a study where healthy volunteers (12 men, 12 women) received a single oral dose of 100 mg ciprofloxacin. The statistical methods were complex but the results of the study demonstrated that women had higher exposure to ciprofloxacin even after adjustment for body weight [4].In contrast, results from a multiple-dose pharmacokinetic study in healthy volunteers (12 men, 12 women) suggest that patient’s sex has no influence on ciprofloxacin pharmacokinetics after correction for body weight [5]. Two other single-dose pharmacokinetic studies in healthy volunteers (22 men, 18 women) show similar results [6, 7].According to the manufacturer, adult dosing is not based on bodyweight [8]. This may bring a risk for subtherapeutic concentrations in men and an increased risk for dose related adverse events in women.

Effects

For quinolones, AUC/MIC correlates best to therapeutic response, both in animal and in vitro kinetic models [9].Resistance patterns for pathogens often differ between populations. A Dutch study comparing resistance in urinary samples (917 from women, 560 from men) found no difference between men and women in E.coli susceptibility to ciproflocaxin [10, 11]. An American study of urinary E. coli isolates (2274 men, 32 265 women) has described age- and sex-specific antibiotic susceptibility patterns for ampicillin, amoxicillin clavulanate, ciprofloxacin, nitrofurantoin and trimethoprim-sulfamethoxazole. Ciprofloxacin susceptibility was similar in men and women (93.2% vs. 95.9%). Age-specific susceptibilities differed between men and women for all antibiotics studied except trimethoprim-sulfamethoxazole. However, the magnitude of the observed differences was generally less than 5% and the authors suggest that they may not represent clinically meaningful differences [12]. In contrast to this a Portuguese retrospective analysis of urinary samples (34 898 (22%) from men and 120 691 (78%) from women) ciprofloxacin resistance was more common in male urinary samples positive for E. coli, P. mirabilis, Klebsiella spp, P. vulgaris, Enterobacter spp, and Providencia spp [13]. An Iranian study report higher ciprofloxacin sensitivity in urine samples from girls/women with urinary tract infection caused by E. coli, K. pneumonia, Enterococcus spp., or Staphylococcus spp. [14].In some settings urine cultures to identify pathogens and resistance pattern cannot always be obtained and therapy of urinary tract infections then has to be empirical. A Brazilian study analyzed urine isolates to identify suitable empirical therapy options for cystitis and urinary tract infections in relation to patient’s sex and age (1098 men, 8700 women). Drug classes analyzed was ampicillin, nitrofurantoin, fluoroquinolones (ciprofloxacin and levofloxacin), trimethoprim-sulfamethoxazole, gentamicin, and ceftriazone/cefotaxime. Women exhibited higher susceptibility values for all drug classes studied than men. For women in any age group, only nitrofurantoin and gentamicin provided adequate activity for empirical therapy (> 80% susceptibility). For men in any age group, only gentamicin was suitable for empirical therapy. In women aged over 60 years, few suitable empirical treatment options were identified [1].

Adverse effects

Fluoroquinolones has been associated with prolonged QT-interval and a risk of Torsade de Pointes ventricular tachycardia. Ciprofloxacin appears to be associated with the lowest risk for QT prolongation and the lowest TdP rate [15]. Risk factors of drug-induced ventricular arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation [16].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).