Die Liquorgängigkeit von Ofloxacin (Tarivid®) bei nicht entzündeten Meningen*

Rh, Staffensky; Stolke, D.; Malottke, R

doi:10.1055/s-2008-1053568

Cited by 1 publication

(3 citation statements)

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“…A nonlinear plasma-CSF transit dependent on the concentration of drug in plasma has been observed with ciprofloxacin in rats, which may have been caused by a carrier-mediated transport from CSF to blood (8). In contrast, the CSF ofloxacin concentrations measured in the present study were approximately twofold greater than those found after administration of the first dose of 200 mg to subjects with uninflamed meninges (2,20); i.e., at doses of 200 and 400 mg, passage from serum to CSF was approximately linear in humans.…”

Section: Discussioncontrasting

confidence: 49%

“…In subjects with inflamed and uninflamed meninges, ready passage of ofloxacin into the cerebrospinal fluid (CSF) has been observed after administration of an oral or intravenous (i.v.) dose of 200 mg (2,15,20,21). The concentrations in CSF were, however, not high enough to be relied upon for use in treating central nervous system (CNS) infections caused by the staphylococci predominantly involved in ventriculitis (2,15,20,21 Table 1).…”

mentioning

confidence: 99%

“…dose of 200 mg (2,15,20,21). The concentrations in CSF were, however, not high enough to be relied upon for use in treating central nervous system (CNS) infections caused by the staphylococci predominantly involved in ventriculitis (2,15,20,21 Table 1). Patients with CNS infections or impaired renal function (creatinine level in serum, >1.2 mg/dl) were not included.…”

mentioning

confidence: 99%

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Kinetics of ofloxacin and its metabolites in cerebrospinal fluid after a single intravenous infusion of 400 milligrams of ofloxacin

Nau

Kinzig

Dreyhaupt

et al. 1994

Antimicrob Agents Chemother

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Ofloxacin has been reported to diffuse readily into the cerebrospinal fluid (CSF) in subjects with both inflamed and uninflamed meninges. However, with moderately susceptible bacteria, ofloxacin concentrations in CSF may be subtherapeutic after administration of an intravenous (i.v.) dose of 200 mg. For this reason, the kinetics of a higher dose of ofloxacin in CSF was studied with humans. Six patients with occlusive hydrocephalus caused by cerebrovascular diseases who had undergone external ventriculostomy received 400 mg of ofloxacin i.v. over 30 mmin. Serum and CSF samples were drawn repeatedly. Serum from 12 healthy volunteers was sampled repeatedly after they had received 400 mg of ofloxacin i.v. over 60 min. Ofloxacin, ofloxacin-N-oxide, and N-desmethyl-ofloxacin concentrations were determined by high-pressure liquid chromatography with fluorescence detection. The maximum ofloxacin concentrations in the serum of the patients ranged from 7.36 to '1.6 mg/liter (mean, 9.55 mg/liter), the apparent volume of distribution/body weight was 0.96 to 1.19 liters/kg (mean, 1.11 liters/kg), and the total body clearance was 115 to 280 ml/min (mean, 192 ml/min). In healthy volunteers, the volume of distribution/body weight and the total body clearance were higher and amounted to 1.27 ± 0.18 liters/kg and 217 ± 43 ml/min (means ± standard deviations), respectively. These differences were attributed to the older ages of the patients than the volunteers. In the CSF of patients, maximum concentration's of 1.00 to 2.85 mg/liter (mean, 2.04 mg/liter) were observed 0.5 to 4 h following'the completion of the ofloxacin infusion. Ofloxacin elimination from CSF was slightly slower than that from serum (half-lives, 4.33 to 10.02 versus 4.27 to 9.14 h). The overall penetration of ofloxacin into CSF, as expressed by the ratios of the areas under the concentration-time curves, amounted to 0.59 to 0.81 (mean, 0.65). The'more hydrophilic metabolites ofloxacin-N-oxide and N-desmethyl-ofloxacin passed less readily than ofloxacin into the CSF. In conclusion, the concentrations in CSF attained after a single i.v. infusion of 400 mg of ofloxacin in the absence of meningeal inflammation appear to be high enough to' inhibit the growth of most staphylococci and members of the family Entrobacteriaceae, which are often involved in CSF shunt infections. Yet, in view of pharmacodynamic studies suggesting a peak concentration in CSF of at least 10-fold the MIC, the use of ofloxacin for central nervous system infections is optimal only with highly susceptible pathogens (MIC, <0.12 mg/liter).Ofloxacin is a moderately lipophilic quinolone with an octanol-water partition coefficient of 0.41 at pH 7.0, 0.33 at pH 7.2, and 0.28 at pH 7.3 (1, 7, 22) and a molecular mass of 361.4 Da. It is active against gram-positive and gram-negative bacteria. Its antibacterial spectrum may allow ofloxacin to be used for the therapy of ventricular shunt infections. In subjects with inflamed and uninflamed meninges, ready passage of ofloxacin into the cerebrospinal fluid (...

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Section: Discussioncontrasting

confidence: 49%