Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers

Abstract

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) Ofloxacin is a fluorinated quinolone exhibiting a marked bactericidal effect by inhibiting DNA gyrase (13, 21). Ofloxacin is active against a wide spectrum of microorganisms, including gram-positive bacteria (11,23, 24). Moreover, it is one of the first drugs allowing oral treatment of infections caused by Pseudomonas aeruginosa (4).Ofloxacin shows therapeutically valuable pharmacokinetic properties such as a medium-range elimination half-life, almost complete bioavailability, negligible metabolism, and predominant renal excretion (9, 11).Since the target sites of antibiotics are predominantly located in the tissues, suitable tissue penetration is also mandatory. Lockley et al. (8) determined ofloxacin cantharides blister fluid (CBF) levels after a single oral dose of 600 mg. Kalager and co-workers (6) used the suction blister method to compare tissue levels in the fasting and nonfasting state (ofloxacin, 300 mg orally).In general, however, ofloxacin is not administered as a single dose but is administered repeatedly for 7 to 10 days. Thus, ofloxacin levels in serum and blister fluid after repeated drug intake are of particular interest. It was the aim of this study to compare ofloxacin levels in the fluids of noninflamed tissues (suction blister fluid [SBF]) (7,20) of an allergy to quinolone carboxylic acids. The study protocol was approved by the local ethics committee, and written informed consent was obtained from each volunteer. During the investigation period, the intake of other drugs and the ingestion of alcohol or caffeine were not allowed.

Pharmacokinetics of isoniazid with or without ofloxacin

“…Fujita et al (1995) in their studies on patients with renal impairment had reported a ratio of 1:1 for saliva to serum concentrations. However, Warlich et al (1990) have reported a ratio of 0.6 and a close relation of levels in the saliva and serum (r= 0.99), which is consistent with our findings. The mean saliva/plasma (S/P) ratio of ofloxacin was around 0.6 and this remained the same when ofloxacin was given in any combination.…”

Isoniazid Pharmacokinetics in the Presence of Ofloxacin and Norfloxacin Antibiotics

“…Fujita et al 24 in their studies on patients with renal impairment had reported a ratio of 1:1 for saliva to serum concentrations. However, Warlich et al 25 have reported a ratio of 0.6 and a close relation of levels in the saliva and serum (r 5 0.99), which is consistent with other findings. The mean S/P ratio of INH was around 0.15 and this remained the same when INH was given in any combination.…”

Ofloxacin Clinical Pharmacokinetics

“…The coefficients of variation (between-day and within-day) in serum, saliva and blister fluid were less than 3.6% (Warlich et al 1990).…”

“…Oral bioavailability of ofloxacin appears to be complete, with 95 to 100% absorbed (Lode et al 1987). Peak serum concentrations are attained rapidly (range 0.5 to 3h) [Bitar et al 1989;Leroy et al 1987;Lode et al 1987;Verho et al 1985;Warlich et al 1990]. The administration of ofloxacin with food delays the time to maximum concentration (tmax) but does not alter the extent of absorption (H6ftken et al 1988;Leroy et al 1987).…”