Ciprofloxacin clearance

The pharmacokinetics of intravenous ciprofloxacin have been studied in intensive care unit patients during continuous venovenous hemofiltration (n — 5) or hemo-diafiltration (n — 5) (67). Ciprofloxacin clearance was not altered. A dosage of 400 mg/day was sufficient to maintain effective drug plasma concentrations in patients undergoing continuous renal replacement therapy. 

Ciprofloxacin (400 mg IV q8h and adjust for creatinine clearance) or levofloxacin (750 mg IV qd and adjust for creatinine clearance)... 

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. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

All quinolones interact with multivalent cations, forming chelation complexes resulting in reduced absorption. Major offenders are antacids vitamins containing calcium and iron can also be problematic. All fluoroquinolones interact with warfarin, didanosine (ddi), and phenytoin, resulting in decreased absorption or metabolism. Ciprofloxacin and other second-generation drugs interact with theophylline by decreasing its clearance, which leads to theophylline toxicity. 

Ciprofloxacin Inhibits DNA Bactericidal Urinary tract Oral, IV mixed clearance (half-life 4 h) ... 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

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. 

Renal clearance of ciprofloxacin averages 300 179 mL/min in adults with normal renal function, and the drug is 16-43% bound to serum protein in vitro. It crosses the placenta and is distributed into the amniotic fluid in humans. The usual human dosage has not revealed evidence of harm to the fetus. 

Quinolone antimicrobials inhibit specific isoenzymes of P450 responsible for the metabolism of methylxanthines thus the clearance of theophylline is reduced by ciprofloxacin. 

Ciprofloxacin Theophylline Reduced clearance of theophylline Decrease dose of theophylline avoid... 

Fluoroquinolones are potent inhibitors of hepatic cytochrome P450 isozymes (150). They inhibit theophylline metabolism, and accumulation of theophylline has led to seizures (151). Theophylline clearance is reduced by about 10% by norfloxacin, 30% by ciprofloxacin, and 70% by enoxacin (152-162). In a comparison of grepa-floxacin (400 and 600 mg/day) and ciprofloxacin, increased theophylline concentrations associated with clinical symptoms were found with both doses of grepa-floxacin but not in patients taking ciprofloxacin (17). The dosage of theophylline should be reduced when a quino-lone is given. 

Schwartz J, Jauregui L, Lettieri J, Bachmann K. Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum. Antimicrob Agents Chemother 1988 32(l) 75-7. 

Interactions of macrolides with triazolam and midazolam are clinically important. Increased serum concentration, AUC, and half-life, and reduced clearance have been documented (93,94,118). These changes can result in clinical effects, such as prolonged psychomotor impairment, amnesia, or loss of consciousness (95). No interactions between ciprofloxacin and diazepam have been reported (96). 

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]. 

A study of the pharmacokinetics of orally administered ciprofloxacin in elderly (63-76 years) and young volunteers (22-34 years) without renal impairment, revealed in the elderly group a decreased renal clearance of the quinolone with no differences detected in the terminal half-life (3.5 hours). This was accompanied, however, by a surprising increase in the absolute availability of the drug [226]. The authors cautioned about the need for a reduction of oral dosage of ciprofloxacin in the elderly population. 

Ljungberg B, Nilsson-Ehle I. Pharmacokinetics of ciprofloxacin in the elderly increased oral bioavailability and reduced renal clearance. Eur J Clin Microbiol Infect Dis. 1989 Jun 8(6) 515-20. 

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. 

The systemic clearance of ciprofloxacin in sheep, horses, dogs and pigs is in... 

Norfloxacin and ciprofloxacin decrease the systemic clearance of theophylline to an extent that could be of clinical significance (Prince et al.r 1989). The effect of the interaction can be avoided by adjusting the dosage rate of theophylline in accordance with the decreased clearance so that steady-state plasma theophylline concentrations remain within the therapeutic range (6-16 pig/mL). 

Fluoroquinolones are used in the treatment of purulent bronchitis and pneumonia and are hence likely to be administered concomitantly with theophylline. Drugs such as enoxacin and ciprofloxacin have been shown to reduce theophylline clearance by inhibiting metabolism. Lomefloxacin on the other hand has been shown to have no clinically significant effect on theophylline metabolism (40, 41). 

Pearson PA, Hainsworth DP, Ashton P. Clearance and distribution of ciprofloxacin after intravitreal injection. Retina 1993 13 326-330. 

The bioavailability of oral or parenteraUy administered ciprofloxacin was not affected in pahents and rats with renal insufficiency [198]. The renal clearance of... 

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