Ciprofloxacin elimination

The complete degradation of sulfamethoxazole was also reported within 14 days with P. chrysosporium, Bjerkandera sp. R1 and B. adusta [4], although, contrary to the reports of enzymatic transformation, metabolites were not identified. Partial removal (from 30% to 55%) of sulfamethoxazole from activated-sludge-mixed liquor and the effluent of a WWTP was demonstrated at bench scale within 5 days with P. chrysosporium propagules entrapped in a granular bioplastic formulation [25]. This approach was also successful in the partial elimination of other kinds of antibiotics, eg., ciprofloxacin (see below) and the macrolide erythromycin. 

The good bioavailability of orally administered ciprofloxacin obviates the need for the more expensive intravenous formulation. I.v. ciprofloxacin is only given to patients who have severe sepsis or severe nausea and vomiting. Ciprofloxacin s elimination is 50% hepatic and 50% renal. Therefore, dose reduction is recommended only in case creatinine clearance drops to < 10 ml/min. Prevention of food-borne disease requires efforts at many levels. Monitoring safety of food processing, vector control, surveillance of outbreaks, education on personal hygiene and improving sanitation and access to safe water supplies are all necessary measures to reduce the incidence of GTI. 

To prevent secondary cases of meningococcal disease prophylaxis with rifampicin 600 mg orally twice daily for two days is recommended for close contacts with the index case. A single dose of 500 mg ciprofloxacin orally is also effective in eliminating nasopharyngeal carriage of N. meningitidis. 

Following oral administration to animals, enrofloxacin is well absorbed and widely distributed to all tissues, with highest concentrations in liver and kidney. Elimination is rapid via both urine and feces. Total enrofloxacin-related residues in urine are mainly composed of enrofloxacin, enrofloxacin amide, and ciprofloxacin and, to a lesser extent, from oxociprofloxacin, dioxociprofloxacin, desethy-lene ciprofloxacin, desethylene enrofloxacin, /V-formyl ciprofloxacin, oxoen-rofloxacin, and hydroxy oxoenrofloxacin. 

The pharmacokinetics of enrofloxacin and its active metabolite, ciprofloxacin, have been further extensively studied in sea bass after treatment by oral gavage or water, at a temperature of 15 C (157). Enrofloxacin was absorbed and eliminated slowly after oral administration to the sea bass. Following bath treatment, enrofloxacin efficiently penetrated fish tissues but it was poorly metabolized compared with mammals. On the other hand, ciprofloxacin was generally detected in very low concentrations (less than 0.02 ppm) in plasma samples after both oral and bath treatment. Liver levels of ciprofloxacin were found to be 0.12 ppm after a 5 ppm bathing for 24 h, 0.06 ppm after a 10 ppm bathing for 8 h, and 0.33 ppm after a 50 ppm bathing for 4 h, suggestive of hepatic metabolism of enrofloxacin. 

Probenecid has been reported to inhibit renal elimination of many drugs acyclovir (325,326), allopurinol (327), bumetanide (328), cephalosporins (329-334), cidofovir (335), ciprofloxacin (336), famotidine (337), fexofenadine (338), furosemide (339), and oseltamivir (Ro 64-0802) (340). Recent studies have elucidated that probenecid is a potent inhibitor of renal organic anion transporters (OAT1 and OAT3) with the Ki values lower than the unbound plasma concentration of probenecid, indicating the interaction with probenecid includes inhibition of the basolateral uptake process mediated by OAT1 and/or OAT3. 

Renal clearance accounts for 61% of the total body clearance of ciprofloxacin in humans (350). Coadministration of probenecid reduces the total body and renal clearance to 59% and 36% of the control value, respectively, but has no effect on the nonrenal clearance (336). The transporters involved in the renal elimination of ciprofloxacin remains unknown. 

Jaehde U, Sorgel F, Reiter A, et al. Effect of probenecid on the distribution and elimination of ciprofloxacin in humans. Clin Phamacol Ther 1995 58 532-541. 

Mannheim market a combination of two antibiotics for sequential use (BM cycle) and quinolones such as ciprofloxacin (Schmitt et al., 1988) and MRA (available from Flow Laboratories for use at 0.5-10 fig/ml) are very effective at eliminating mycoplasma. The quinolones inhibit the prokaryotic DNA gyrase. 

Ciprofloxacin is eliminated by renal and non-renal mechanisms. The drug is partially metabolized in the liver by modification of the piperazinyl group to atleast four metabolites. These metabolites, which have been identified as desethylene-ciprofloxacin, sulfo-ciprofloxacin, oxo-ciprofloxacin, and A-acetyl-ciprofloxacin, have microbiological activities that are less than that of the parent drug, but may be similar to or greater than that of some other quinolones [4, 8, 9]. 

Rifampicin (600 mg orally twice daily for 2 days) should be administered to patients with meningococcal or H. influenzae meningitis who have not been treated with ceftriaxone, as soon as they can tolerate oral medication to eliminate nasal carriage of the organisms. Alternatively ciprofloxacin (500 mg orally stat) has proven efficacy for elimination of nasal carriage of meningococcus only. 

A significant fraction of each drug is excreted unchanged in the urine (by glomerular filtration and tubular secretion, e.g. norfloxacin and ciprofloxacin). Sparfloxacin and trovafloxacin have significant non-renal elimination pathways. Hepatic metabolism also takes place (e.g. nalidixic acid being converted to an active metabolite). 

Campylobacter jejuni. Erythromycin or ciprofloxacin by mouth will eliminate the organism from the stools and a 5-day course is worth giving early in the illness if it is severe. 

Vibrio cholerae. The cause of death in cholera is electrolyte and fluid loss in the stools and this may exceed 11/h. The most important aim of treatment is prompt replacement and maintenance of water and electrolytes with oral or intravenous electrolyte solutions. Doxycycline, given early, significantly reduces the amount and duration of diarrhoea and eliminates the organism from the faeces (thus lessening the contamination of the environment). Carriers may be treated by doxycycline by mouth in high dose for 3 days. Ciprofloxacin may be given for resistant organisms. 

In order to eliminate both dividing and non-dividing bacteria, a fluoroquinolone antibiotic, ciprofloxacin, has been associated with PIBCA and PIHCA nanospheres. In an animal model of persisting Salmonella infection, although an effect on the early phase of the infection was observed, neither free nor nanosphere-bound ciprofloxacin was able to eradicate truly persisting bacteria. ... 

Methotrexate elimination can be delayed by ciprofloxacin. Two adolescents with malignant diseases had reduced elimination of methotrexate (12 g/m 4-hourly) when they took ciprofloxacin 500 mg bd (74). 

Based on their predominant renal elimination, dosage adjustment is necessary in the presence of renal disease for ciprofloxacin, gatifloxacin, levofloxacin, and sitaflox-acin (124). 

The bioavailability of oral or parenterally administered ciprofloxacin was not affected in patients and rats with renal insufficiency [222]. The renal clearance of the quinolone, however, was reduced resulting in a prolonged half-life [223-225]. Thus, a reduction of 50% in the dose of ciprofloxacin has been recommended when the creatinine clearance is between 10 and 30 ml/ min/1.73 m [224]. Of interest, it has been suggested that there may be a compensatory transin-testinal elimination of ciprofloxacin in patients and rats with reduced renal function [224, 225]. 

Rohwedder R, BerganT, Thorsteinsson SB, Scholl H.Transintestinal elimination of ciprofloxacin. Chemotherapy. 1990 36(2) 77-84. 

Mowles JM (1988) The use of Ciprofloxacin for the elimination of mycoplasmas from naturally infected cell lines. Cyto-technology 1 355-358. 

Ciprofloxacin is well absorbed in the gastrointestinal tract. Serum concentration peaks in 1.5-2 h postingestion. The elimination half-life with normal renal function is 4h. Ciprofloxacin is 20-40% bound to serum proteins and distributed widely throughout the body. Four metabolites in human urine have been identified, which account for 15% of an oral dose. The metabolites have antimicrobial activity, which are less active than the parent compound of ciprofloxacin. Ciprofloxacin inhibits CYP3A4 enzyme system. 

Enrofloxacin is mainly eliminated by hepatic metabolism, and systemic clearance of the drug varies between species. In sheep, horses, dogs and pigs the average clearance of enrofloxacin is in the range 5.75-8.56 mL/min kg, while enrofloxacin clearance (mL/min kg) differs more widely between other species rabbits (17.9), llamas (12.0), chickens (3.3), turkeys (8.9), houbara bustard (5.7) and fingerling rainbow trout (Oncorhynchus mykiss) at 15°C (1.25). Systemic clearance of enrofloxacin represents mainly hepatic clearance composed of a variety of metabolic pathways, which include N-deethylation to ciprofloxacin. 

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