Pharmacokinetics of ofloxacin after parenteral and oral administration

The pharmacokinetics and bioavailabiity of ofloxacin in 20 healthy male volunteers were studied in an open-label, randomized, two-way crossover study. Ofloxacin (400 mg) was administered either as a 1-h infusion or as an oral tablet. The mean peak concentration after intravenous infusion was 4.30 0.69 ,ug/ml, and that after oral administration was 3.14 ± 0.53 ,ug/mI, occurring 1.74 + 0.57 h after dosing. The bioavailability (F) of the oral dosage form of ofloxacin was virtuaUy identical to that of the intravenous form (F = 105% 7%). This complete bioavailability of ofloxacin is supportive of the use of the oral dosage form for the treatment of infections in hospitalized patients either as a replacement for intravenous ofloxacin therapy or in streamlining therapy from the intravenous to the oral route.Ofloxacin is a synthetic, fluorinated carboxyquinolone active against members of the family Enterobactericeae and gram-positive organisms. Its favorable pharmacokinetic features include good oral absorption and lack of metabolism resulting in decreased drug interaction. The presence of the methyl piperazine ring in ofloxacin probably leads to enhanced oral absorption and a long half-life (properties shown by other quinolones such as pefloxacin, fleroxacin, and difloxacin). Pharmacokinetic disposition and bioavailability have been previously studied in different study populations, and the bioavailability of ofloxacin has been reported to be 80 to 90% (1, 2, 4, 5, 7). There is a paucity of data, however, directly comparing oral (p.o.) and intravenous (i.v.) dosage forms in the same population. The present study was undertaken to evaluate the bioavailabilities of orally and parenterally administered ofloxacin in normal volunteers. An accurate determination of bioavailability is necessary for considering the use of oral ofloxacin in place of the parenteral form in the treatment of hospitalized patients.On the basis of laboratory tests (serum chemistry, hematology, urinalysis), medical history, and physical examination, 20 healthy male volunteers (age, 25 ± 4.6 years; weight, 74.5 ± 7.87 kg; height, 178.3 ± 5.92 cm [mean ± standard deviation]) were enrolled in this study after giving written informed consent. No alcohol or concomitant medication was allowed 72 h prior to the initial administration of the dose and for the entire duration of the study. All subjects reported to the study site at least 12 h prior to the administration of the initial dose, remained within the facility for 36 h after each dose, and returned to the study site for the 48-h scheduled blood draw. Subjects were dosed in the mornings of day 1 and day 8. Subjects fasted at least 8 h prior to each dose and remained fasted for 2 h postdose. Water was permitted ad lib until 2 h prior to and 2 h after dosing. Tablets containing 400 mg of ofloxacin (FD 18489-BS-22) and 10-ml single-dose vials containing 400 mg of ofloxacin (FD 18489-* Corresponding author. BR-45) for parenteral use were provided by Ortho Pharmaceutical Corporation.The tablets were admin...

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confidence: 99%

Bioavailability and pharmacokinetics of ofloxacin in healthy volunteers

Yuk

Nightingale

Quintiliani

et al. 1991

“…tested (6,11). In view of the satisfactory in vitro activities of these two quinolones, clinical trials to verify their efficacy in treating brucellosis are warranted.…”

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confidence: 99%

Comparative in vitro activities of ofloxacin, difloxacin, ciprofloxacin, and other selected antimicrobial agents against Brucella melitensis

Khan

Dizon

Kiel

1989

The in vitro activities of three quinolones (ofloxacin, difloxacin, and ciprofloxacin) were compared with those of trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and rifampin against 47 Brucella melitensis strains. Ofloxacin was the most active of the test antimicrobial agents. It inhibited 90% of B. melitensis strains at a concentration of 0.02 ,ug/ml.Ofloxacin, difloxacin, and ciprofloxacin are quinolones which are active in vitro against a broad spectrum of microorganisms (4,12,13). This study was conducted to compare the in vitro activities of these three quinolones with those of trimethoprim-sulfamethoxazole, streptomycin, tetracycline, and rifampin against Briucella melitensis isolates.Standard powders with known potencies were obtained as

“…Tubular transport of enoxacin, norfloxacin, ciprofloxacin, and ofloxacin has also been inferred by high CLR/CLCR ratios or has been confirmed by demonstration of significant reductions in CLR when coadministered with probenecid, an inhibitor of anionic tubular transport (5,18,23,25,28,29). Even fleroxacin, which has a CLR/CLCR ratio below unity, appears to have probenecid-sensitive tubular secretion (22).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of temafloxacin in humans after multiple oral doses

Granneman

Carpentier

Morrison

et al. 1992

The multiple-dose pharmacokinetics and tolerance of temafloxacin, a new fluoroquinolone antibacterial agent, were evaluated in healthy volunteers. Temafloxacin was found to be well tolerated when administered orally every 12 h for 7 days at doses of 100, 200, 300, 400, 600, and 800 mg. Steady-state maximum and minimum concentrations in plasma were proportional to dose, averaging slightly over 1.0 and 0.5 microgram/ml/100 mg administered. Analyses of variance found no significant differences among the dosage groups in total apparent clearances (CLT/F), renal clearances (CLR), or nonrenal clearances, which averaged 197, 119, and 78 ml/min, respectively. The half-life increased slightly with dose, averaging 8.4 h overall. The extent of absorption of temafloxacin was quite reproducible, with day-to-day intrasubject variability in minima averaging under 10%. Renal glomerular filtration of unbound drug was the dominant elimination process; however, tubular secretion and reabsorption also appear to occur. Secretion was estimated to account for about 12% of CLT/F during a regimen of 600 mg every 12 h. CLR was relatively constant for urine flow rates above 1 ml/min, but reabsorption appeared to occur under low-flow conditions, resulting in day-versus-night differences in CLR. Intersubject variability in CLT/F over the eightfold range in dosage was only 20%, and 60% of this variance was accounted for by differences in body surface area (or lean body mass), concentration in plasma, and urine flow rate. Overall, it appears that the pharmacokinetics of temafloxacin are essentially linear, reproducible within a subject, and predictable among subjects.