Transfer kinetics of pefloxacin into cerebro-spinal fluid after one hour iv infusion of 400 mg in man

J, Dow; Chazal, J.; Frydman, Armand; Janny, P; Woehrle, R; Djebbar, F.; Gaillot, J.

doi:10.1093/jac/17.suppl_b.81

Cited by 32 publications

(9 citation statements)

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“…The AUCcsF/AUCS of ofloxacin (present study), pefloxacin (as estimated previously [3]), and ciprofloxacin (10) compared well with the tears/plasma AUC ratios of ofloxacin in humans (17). (3,10) indicate that the entry of quinolones into CSF in the absence of meningeal inflammation in humans also is predominantly determined by lipophilicity.…”

Section: Discussionsupporting

confidence: 82%

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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: Discussionsupporting

confidence: 82%

“…(3,10) indicate that the entry of quinolones into CSF in the absence of meningeal inflammation in humans also is predominantly determined by lipophilicity.…”

Section: Discussionmentioning

confidence: 99%

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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“…The rate of transfer of N-demethyl-pefloxacin across the blood-CSF barrier is low as its Cmax in the CSF does not exceed 0.2 mg/L. [86] In patients with meningitis the ratio of AVC for CSF : AVC for serum was 0.53 after the first 400mg dose and 0.66 at steady-state. !85] Analogous data were reported by Wolff et al [84] in patients with meningitis or ventriculitis.…”

Section: Cerebrospinal Fluidmentioning

confidence: 99%

Pefloxacin Clinical Pharmacokinetics

Bressolle

Gonçalves

Gouby

et al. 1994

Clinical Pharmacokinetics

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Pefloxacin has a broad spectrum of activity against a great number of Gram-negative and Gram-positive bacteria. It is also capable of penetration into cells, yielding high tissue:serum ratios, with implications for the treatment of infections caused by intracellular pathogens. Pefloxacin is well absorbed from the gastrointestinal tract. Its elimination half-life ranges from 6.2 to 12.4 hours. After repeated administration, a major change in pharmacokinetic parameters is observed. Pharmacokinetic parameters are minimally altered or not altered in patients with impaired renal function. Altered plasma pharmacokinetics in patients with liver insufficiency and in elderly patients are observed, so dosage adjustments are necessary. In addition, pefloxacin interacts with a number of other compounds at hepatic (e.g. theophylline and cimetidine) and gastrointestinal (e.g. antacids) sites. With the exception of saliva, cerebrospinal fluid, aqueous humor, vitreous fluid and amniotic fluid, body fluid concentrations reach plasma concentrations. Studies on tissue penetration show that concentrations exceeding plasma concentrations are obtained in most tissues. The highest tissue:plasma concentration ratios are achieved in lung and kidney, whereas concentrations in fat are considerably lower than those in plasma.

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“…The penetration of ofloxacin and other fluoroquinolones in the cerebrospinal fluid (CSF) has been studied in inflamed and noninflamed meninges from a small number of patients, and the concentrations were found to be higher than the MICs for most susceptible gram-negative bacilli (2,3,13,14).…”

mentioning

confidence: 99%

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

Bitar

Claes

Auwera

1989

Antimicrob Agents Chemother

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The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 ,ig/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 pg/ml) or 1 to 2 h after oral administration (1.7 to 4 ,ug/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae.

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Transfer kinetics of pefloxacin into cerebro-spinal fluid after one hour iv infusion of 400 mg in man

Cited by 32 publications

References 0 publications

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

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

Pefloxacin Clinical Pharmacokinetics

Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally

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