Pharmacokinetics and tolerance of lomefloxacin after sequentially increasing oral doses

Morrison, P. J.; Mant, Timothy; Norman, G. T.; Robinson, J. A.; Kunka, Robert L.

doi:10.1128/aac.32.10.1503

Cited by 75 publications

(33 citation statements)

References 7 publications

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“…Pharmacokinetic studies in normal volunteers showed that following oral administration, lomefloxacin is rapidly absorbed into the blood, distributed into peripheral tissues, and primarily excreted unchanged at high concentrations into urine (6,8). Lomefloxacin has a half-life (t1/2) of approximately 7 to 8 h in normal volunteers (6,8).…”

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confidence: 99%

Pharmacokinetics of lomefloxacin in renally compromised patients

Blum

Schultz

Schentag

1990

Antimicrob Agents Chemother

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The single-dose pharmacokinetics of orally administered lomefloxacin (400 mg) were studied in normal subjects and in patients with various degrees of renal function. The subjects were classified by creatinine clearance (CLCR) normalized for body surface area: group 1, CLCR of >80 ml/min/1.73 mi2; group 2, CLCR of 80 to >40 ml/min/1.73 M2; group 3, CLCR of 40 to >10 ml/min/1.73 M2; and group 4, CLCR of <10 mllmin/1.73 m2. Each group consisted of eight subjects. The pharmacokinetics of lomefloxacin were significantly influenced by renal function. There were significant differences in the elimination rate constant, half-life, area under the concentration-time curve from 0 h to infinity, apparent total drug clearance, renal clearance, and apparent nonrenal drug clearance between the four renal function groups. Mean half-lives for groups 1, 2, 3, and 4 were 8.09, 9.11, 20.90, and 44.25 h, respectively. There were no significant differences between the renal groups for maximum concentration of the drug in serum and apparent volume of distribution. Age had no apparent effect on lomefloxacin disposition. There was a significant relationship between CLCR and lomefloxacin total body clearance (r = 0.92, P = 0.001) and renal clearance (r = 0.94, P = 0.001). Despite a predominate renal route of elimination, nonrenal lomefloxacin clearance significantly decreased with decreasing renal function (r = 0.72, P = 0.001). Mean lomefloxacin excretion rates over 48 h were 60.7, 56.0, 29.1, and 1.0% of the administered dose for groups 1, 2, 3, and 4, respectively. Mean glucuronide excretion rates over 48 h were 7.8, 6.3, 10.0, and 0.6% of the administered dose for groups 1, 2, 3, and 4, respectively. Hemodialysis had no effect on lomefloxacin concentrations in plasma. In patients with normal to moderate renal function, 400 mg of lomefloxacin per day should provide therapeutic concentrations in blood. The lomefloxacin dose should be reduced to 200 mg/day as the CLCR fails below 30 ml/min/1.73 M2. No additional dosage adjustments appear to be necessary for hemodialysis patients.

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confidence: 99%

Pharmacokinetics of lomefloxacin in renally compromised patients

Blum

Schultz

Schentag

1990

Antimicrob Agents Chemother

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“…Following multiple oral administrations of lomefloxacin to patients scheduled for elective prostate surgery, concentrations in serum during the perioperative period (1 to 6 h postdose) exhibited a gradual decline, consistent with the prolonged elimination half-life (approximately 7 h) previously reported from healthy-volunteer studies (11,13,17 15 patients with benign prostatic hyperplasia prior to surgery, partition coefficients ranged from 1.0 to 2.8 over a 6-h period. The results of the present multiple-dose investigation are in general agreement with this preliminary study and with published data for other fluoroquinolones, for which prostate partition coefficients ranged from 0.5 to 6 (2).…”

Section: Discussionmentioning

confidence: 52%

Intraprostatic distribution of lomefloxacin following multiple-dose administration

Kovařík¹,

Hond²,

Hoepelman³

et al. 1990

Antimicrob Agents Chemother

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The ability of lomefloxacin to penetrate and distribute within the human prostate was assessed in 20 patients undergoing elective prostate surgery (18 transurethral prostatic resections and 2 prostatectomies). Subjects were middle-aged to elderly (mean age ± standard deviation, 69.8 ± 8.2 years) with normal hepatic function and with creatinine clearances ranging from 35.8 to 141 ml/min/1.73 M2. Lomefloxacin was administered in 400-mg doses orally every 24 h. Its disposition was characterized following the third dose by obtaining multiple serum samples and intraoperative paired central zone and peripheral zone prostate tissue samples. Lomefloxacin concentrations were determined by a validated high-performance liquid chromatography method with fluorescence detection. Concentrations in serum during the perioperative period declined from 3.1 + 1.0 mg/liter (mean ± standard deviation) at 1 h postdose to 2.3 ± 0.7 mg/liter at 6 h postdose. The time of tissue extraction ranged from 0.1 to 7.1 h postdose. Intraoperative serum lomefloxacin concentrations ranged from 0.5 to 4.8 (median, 2.4) mg/liter, while prostate tissue concentrations ranged from 1.1 to 10.1 (median, 5.4) mg/kg of tissue for the central zone and 0.9 to 6.5 (median, 5.2) mg/kg for the peripheral zone. Intraindividual paired prostate concentrations (central zone versus peripheral zone) were not statistically different. The partition coefficient (ratio of concentration in prostate to concentration in serum) for the central zone was 2.2 +-0.6 (range, 1.2 to 3.1), and for the peripheral zone it was 2.1 + 0.7 (range, 1.2 to 4.2). Lomefloxacin exhibited good penetration into the human prostate with homogeneous intraprostatic distribution following multiple-dose administration.

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“…Some of the third generation fluoroquinolones such as sparfloxacin and lomefloxacin also exhibit increased serum levels and half-life [16,17]. For example, Morrison et al [18] reported maximum lomefloxacin serum levels of 1.11 to 7.46 mg/L for the 100 to 800 mg oral doses, respectively, and a serum half-life of approximately eight hours. Such peak levels and the half-life allows the possibility of single daily dosing as compared to twice-daily dosing for second generation antibiotics such as ciprofloxacin and norfloxacin.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity of Fluoroquinolones Local Clinical Isolates from a Referral Center in Riyadh

1992

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A total of 1,034 clinical isolates from a tertiary care center were tested against six fluoroquinolones, namely norfloxacin, ciprofloxacin, lomefloxacin, sparfloxacin, temafloxacin, and CI-960. Bacteria tested consisted of 579 strains of Enterobacteriaceae, 98 pseudomonads, 51 Acinetebacter, 56 enterococci and 250 isolates of staphylococci. All six fluoroquinolones showed excellent in vitro activity inhibiting >90% of Escherichia coli at an MIC of < 0.03-0.5 mg/L, Klebsiella pneumoniae at 0.12-2.0 mg/L, Enterobacter at 0.12-2.0 mg/L, Serratia marcescens at 0.12-2.0 mg/L, Pseudomonas aeruginosa at 0.5-2.0 mg/L, Staphylococus aureus at < 0.03-1.0 mg/L, and coagulase negative staphylococci at an MIC of 0.12-2.0 mg/L Xanthomonas maltophilia showed some resistance to norfloxacin, ciprofloxacin, lomefloxacin and temafloxacin, but was inhibited by sparfloxacin and CI-960. A majority of isolates of enterococci were resistant to norfloxacin, ciprofloxacin, lomefloxacin and CI-960, but sparfloxacin and temafloxacin inhibited 92% and 82% of these strains, respectively. The newer fluoroquinolones are a major advance in antimicrobial chemotherapy and have evolved from chemical modifications of nalidixic acid [1]. The first breakthrough occurred during the early 1980s when norfloxacin, a second generation quinolone with 6-flourine and 7-piperazine substituents, was synthesized. The enhanced activity of this drug as an orally active agent for urinary tract infections resulted in further development of other fluoroquinolones such as ciprofloxacin and later by third generation quinolones such as lomefloxacin, sparfloxacin, temafloxacin, and CI-960 [2]. The newer 4-quinolone antibacterial agents possess a carboxyl group at position four. The addition of a piperazine at position seven confers increased antimicrobial activity, especially against P. aeruginosa. Fluorination of the nucleus at position six increases antibacterial potency. In fact, the trend in the synthesis of newer third generation agents has been to increase the number of flourine residues. Structural changes of the parent compound (Figure 1) have thus resulted in extended spectrum of activity, better penetration, and improved pharmacokinetic properties.

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Pharmacokinetics and tolerance of lomefloxacin after sequentially increasing oral doses

Cited by 75 publications

References 7 publications

Pharmacokinetics of lomefloxacin in renally compromised patients

Pharmacokinetics of lomefloxacin in renally compromised patients

Intraprostatic distribution of lomefloxacin following multiple-dose administration

Antibacterial Activity of Fluoroquinolones Local Clinical Isolates from a Referral Center in Riyadh

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