Pharmacokinetics of ciprofloxacin in healthy volunteers after oral and intravenous administration

Abstract

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21-35 years; body weight 52-80 kg). Single oral doses of 50, 100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37 +/- 0.49 mg/l (100 mg dose) and 1.97 +/- 0.50 (750 mg dose) were measured 60-75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15 +/- 0.05 mg/l. Taking a breakfast reduced absorption by 15-20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i.v. (20 min infusion period), initial serum concentrations of 4.0 +/- 1.2 mg/l were observed which declined 12 h later to 0.070 +/- 0.025 mg/l. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as M1 and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2 +/- 0.4% of M1 and 5.5 +/- 1.6% of M3.(ABSTRACT TRUNCATED AT 250 WORDS)

Peroral treatment with ciprofloxacin of patients with spinal cord lesion and bacteriuria caused by multiply resistant bacteria

“…hours after intake (T ma J which is comparable to the data of Borner et al (1986), who investigated the pharmacokinetics in non-fasting healthy vo lunteers. Ciproftoxacin is rapidly excreted into the urine and high concentra tions were achieved even within 2 hours of drug intake.…”

“…Ciproftoxacin is rapidly excreted into the urine and high concentra tions were achieved even within 2 hours of drug intake. However, the half-life is considerably shorter in our patients (Table III) than in other studies where it was found to range between 3 and 5 hours (Wingender et al, 1984;Borner et al, 1986). High concentrations of ciproftoxacin were achieved in the urine and in most of the dosing interval by far exceeding the minimal concentrations necessary to inhibit growth of urinary tract pathogens (Wise et al, 1983;Fass, 1983).…”

Pharmacokinetics of ofloxacin after parenteral and oral administration

“…Ciprofloxacin, another parenteral quinolone, has biological half-lives of between 180 and 260 min (3,4,8,13,25), whereas biological half-lives of parenteral enoxacin (306 + 25 min [26]) and parenteral pefloxacin (630 + 90 min) were longer (10,26).…”

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In 10 volunteers, the pharmacokinetics of ofloxacin {HOE 280, DL 8280; (+)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido-[1,2,3-deI [1,4] 1.4 liters/kg of body weight) suggested effective diffusion into the extravascular space. High total and renal clearances indicated primarily renal excretion with additional elimination pathways, such as tubular secretion and extrarenal elimination.

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“…Ofloxacin {HOE 280, DL 8280; (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1,2,3-de] [1,4]benzoxacine-6-carboxylic acid} is a new quinolone carboxylic acid derivative showing a broad antimicrobial spectrum against gram-positive and gram-negative bacteria (1,11,17,22,27). This substance was found to be more active than norfloxacin and pipemidic acid (22), its in vitro antibacterial activity being almost comparable to those of gentamicin, tobramycin, and newer cephalosporins (9,11,27).…”