Dieter Beermann

Absorption Differences of Ciprofloxacin along the Human Gastrointestinal Tract Determined Using a Remote-Control Drug Delivery Device (HF-capsule)

The single-dose absorption kinetics of ciprofloxacin in different regions of the human gastrointestinal tract were investigated using a remote-control drug delivery device (HF-capsule). Doses of 180 to 200 mg ciprofloxacin (as a lactic acid solution) were placed in the HF-capsule and administered to four healthy male adults. The position of the HF-capsule in the gastrointestinal tract was checked via radiographic examination. The release of the solution from the HF-capsule was induced by a radio signal. In each volunteer, the solution was released into five different regions of the gastrointestinal tract: the stomach (B), jejunum (C1), ileum (C2), ascending colon (D1), and descending colon (D2). Two control runs (A1, A2), involving oral administration of the solution, were used as a reference for calculation of area under the curve. The oral administration of a conventional 250-mg tablet (A3) was also studied. The plasma concentration of ciprofloxacin and urine concentrations of ciprofloxacin, desethylene- (M1), sulfo- (M2), and oxociprofloxacin (M3) were determined fluorimetrically by high-performance liquid chromatography. Intraindividual comparisons indicated a progressive decrease in the amount of ciprofloxacin absorbed (100 percent = mean of AUCA1 and AUCA2) from the jejunum (-61 percent, median), ileum (-75 percent), colon ascendens (-90 percent), and colon descendens (-95 percent). Absolute amounts of renally excreted ciprofloxacin and metabolites decreased due to the reduced absorption of ciprofloxacin, but the metabolite pattern was unchanged. It is concluded that the main absorption site for ciprofloxacin is the upper part of the intestinal tract (duodenum, jejunum).

Liquid Chromatographic Analysis of Ciprofloxacin and Ciprofloxacin Metabolites in Body Fluids

Abstract An isocratic HPLC assay procedure for analysis of ciprofloxacin and three metabolites was developed. The procedure requires only dilution of bile, saliva, and urine samples prior to reverse-phase chromatography on a polystyrene-divinylbenzene (PSDVB) column; analysis of serum samples requires a cleanup step on a PSDVB cartridge prior to chromatography. The dependence of chromatographic efficiency on flow rate and temperature was investigated and the accuracy, precision, selectivity, and sensitivity of the procedure were evaluated. The developed procedure was also compared to a modified version of a published ciprofloxacin procedure that requires an octadecyl-silane (ODS) column for chromatographic separation. Similar efficiency, precision, and accuracy were observed with both procedures and both were used for analysis of clinical samples. However, the procedures were used for different purposes. The PSDVB procedure, because of more favorable column selectivity, was used to assay ciprofloxacin and...

Efficacy and safety of higher-dose intravenous ciprofloxacin in severe hospital-acquired infections

In an open prospective study, 54 patients in an interdisciplinary, operative, anesthesiologic intensive care unit were treated with intravenous ciprofloxacin for life-threatening infections. Secondary nosocomial pneumonias were the predominant infection in most patients. A total of 88 causative pathogens were isolated from 50 patients. The most commonly isolated organism was Pseudomonas aeruginosa; Serratia marcescens, Staphylococcus aureus, and Enterobacter sp. were also isolated. Pathogens could not be detected in four patients (three patients with pneumonia, one patient with urinary tract infection). Ciprofloxacin was administered intravenously, either 400 mg every 12 hours or, after a loading dose of 600 mg every 12 hours on Day 1, 400 mg every 12 hours on successive treatment days. A total of 44 patients were treated parenterally, four orally. An additional six patients received ciprofloxacin in both dosage forms as sequential therapy. Serum ciprofloxacin levels were determined by high-performance liquid chromatography in 17 patients. The serum concentrations and the elimination half-life were in accordance with values already published for parenteral doses of 200 and 500 mg ciprofloxacin. Ciprofloxacin clearance was linear even at the high dose (600 mg every 12 hours loading dose) and no cumulative effect was observed. Clinical outcome was very good. Cure was achieved in 21 patients, and clinical improvement occurred in 23 (favorable clinical response rate, 82 percent). Two patients did not respond to therapy, and eight patients were not evaluable. Adverse effects occurred in 12 patients: transient elevation of liver enzymes (seven patients), temporary increase in serum creatinine levels (two), convulsions (two), and exanthem (one). The treatment of severe infections in intensive care patients with higher doses of parenteral ciprofloxacin appears to be considerably more effective than therapy with the doses of intravenous ciprofloxacin recommended to date. Therefore, these preliminary results are the subject of an ongoing double-blind study.

Pharmacokinetics of the active metabolite of the prodrug repirinast in healthy Caucasian volunteers after a single oral dose.

SummaryThe pharmacokinetics of BAY w 8199, the active metabolite of the prodrug repirinast (BAY u 2372), has been investigated after oral administration of 150, 300 and 450 mg repirinast to twelve healthy male Caucasians.Plasma BAY w 8199 concentrations were very variable between subjects. The mean peak level (geom. mean; 1s-range) was 0.14 (0.08–0.25), 0.19 (0.13–0.29) and 0.24 (0.14–0.42) mg/l after the 150, 300 and 450 mg doses, respectively. Peak levels were reached 0.5–2.5 h after drug intake. Terminal half-lives were calculated as 5.9 h (150 mg), 8.0 h (300 mg) and 9.8 h (450 mg).The dose proportionality of the plasma profiles of BAY w 8199 and of its excretion in urine was demonstrated by testing several parameters.About 7.4% of each dose (calculated as BAY w 8199) was excreted in urine over 36 h. The renal clearance of about 27 l/h suggests that BAY w 8199 is excreted by tubular secretion in addition to glomerular filtration.