Pharmacokinetics of ofloxacin after parenteral and oral administration

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-de] [1,4]benzoxacine-6-carboxylic acid) was determined after administration of 25, 50, 100, and 200 mg intravenously (30-min infusion) as well as 200 and 400 mg orally. Concentrations in serum and urine were measured by high-pressure liquid chromatography. Concentrations in serum following different parenteral ofloxacin dosages demonstrated dose dependency with long biological half-lives of 231 to 267 min. Pharmacokinetic parameters were calculated on the basis of open two- and three-compartment models, which yielded nearly identical results. High volumes of distribution (1.2 to 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. After oral administration, absorption was excellent, and the absolute bioavailability following 200 mg of ofloxacin could be calculated at >0.95. Maximal concentrations in serum were attained 1.2 to 1.9 h after dosing; areas under the curve increased in proportion to dose between 200 and 400 mg of oral ofloxacin. The amount of known metabolites (demethyl and N-oxide compounds) excreted in urine reached only 4.3% (intravenously) and 4.0% (orally). Transient headaches in some volunteers were the only side effects registered.