Metabolic interactions of ciprofloxacin

Ludwig, Endre; Graber, H; Székely, Edit; Csiba, A

doi:10.1016/0732-8893(90)90096-e

Cited by 12 publications

(4 citation statements)

References 14 publications

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“…Oral metronidazole 1500mg daily and ciprofloxacin 500mg twice daily were administered simultaneously for 7 to II days to 8 patients with bacterial infections (Ludwig et al 1990). No significant change in ciprofloxacin pharmacokinetics was observed.…”

Section: Ciprofloxacinmentioning

confidence: 97%

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Lau

Lam

Piscitelli

et al. 1992

Clinical Pharmacokinetics

182

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Metronidazole was first introduced for the treatment of trichomoniasis. Its therapeutic use has subsequently been expanded to include amoebiasis, giardiasis and, more recently, anaerobic infections. Most of the early pharmacokinetic studies employed nonspecific assays such as microbiological and chemical assays. These assays were not able to differentiate the parent drug from the metabolites or other interfering substances. Pharmacokinetic data obtained through the use of specific chromatographic techniques provide the basis for this review of recent pharmacokinetic findings concerning metronidazole and other nitroimidazole antibiotics. When given intravenously or orally at usual recommended doses, metronidazole attains concentrations well above the minimum inhibitory concentrations for most susceptible micro-organisms. The drug has an oral bioavailability approaching 100%. Rectal and vaginal administration results in a smaller amount of drug absorption and lower serum concentrations. Metronidazole has limited plasma protein binding but can attain very favourable tissue distribution, including into the central nervous system. The drug is extensively metabolised by the liver to form 2 primary oxidative metabolites: the hydroxy and acetic acid metabolites. The kidney is responsible for the elimination of only a small amount of the parent drug; however, normal excretion of the 2 metabolites is dependent on the integrity of kidney function. The metabolism of metronidazole was found to vary among patient groups. Preterm and term infants have lower total body clearance (CL) and prolonged elimination half-lives. However, children older than 4 years old were observed to have pharmacokinetic parameters similar to those in adults. Reduced CL was also observed in children who are malnourished. Elderly patients have reduced renal excretion of both the parent drug and hydroxy metabolite. Pharmacokinetic parameters in pregnant patients were not significantly different from those in nonpregnant women; however, the drug is distributed into breastmilk and the infant will be exposed to the drug through the nursing mother. Patients undergoing gastrointestinal surgery or having enteric diseases and those who are hospitalised or critically ill also have altered pharmacokinetics. Metabolism of the drug is reduced in patients with liver dysfunction, giving delayed production of metabolites. In contrast, renal failure has little effect on the elimination of the parent drug, but affects the excretion of the metabolites more significantly. Haemodialysis was found to remove a substantial amount of the metronidazole while the effect of peritoneal dialysis was more limited. Energy and protein deficient diets as well as occupational exposure to gasoline did not alter metronidazole pharmacokinetics. However, the effect of alcohol consumption on metronidazole CL requires further study.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Ciprofloxacinmentioning

confidence: 97%

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Lau

Lam

Piscitelli

et al. 1992

Clinical Pharmacokinetics

182

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“…Coadministration of ciprofloxacin 500mg twice daily with cimetidine 250mg 4 times daily or metronidazole 500mg twice daily did not significantly affect the pharmacokinetics of ciprofloxacin , nor did ciprofloxacin affect the pharmacokinetics of either of the other 2 drugs (Ludwig et al 1990). …”

Section: Drug Interactionsmentioning

confidence: 90%

Ciprofloxacin

Wiseman¹,

Balfour²

1994

Drugs & Aging

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Ciprofloxacin belongs to the fluoroquinolone class of antimicrobial agents which primarily inhibit bacterial DNA gyrase. It is effective after oral or intravenous administration, demonstrating potent antibacterial activity against most Gram-negative, and many Gram-positive bacteria. Although most bacterial strains have remained susceptible to the drug, low rates of resistance have been observed in some strains of Pseudomonas aeruginosa and enterococci and higher rates in methicillin-resistant Staphylococcus aureus. Ciprofloxacin attains concentrations in most tissues and body fluids sufficient to inhibit the majority of susceptible pathogens. Its pharmacokinetic profile in the elderly (> or = 65 years) is broadly similar to that reported in younger persons, although plasma concentrations are higher, and renal clearance is decreased in elderly persons. Ciprofloxacin is an effective treatment for those infections most common in elderly patients, including infections of the urinary tract, lower respiratory tract, skin and soft-tissues, and bone and joints, and is an effective agent for prophylaxis in transurethral surgery. Orally administered ciprofloxacin appeared to be at least as effective as alternative orally administered antimicrobial agents (trimethoprim, cotrimoxazole [trimethoprim/sulfamethoxazole], amoxicillin, amoxicillin/clavulanic acid) and also as effective as various parenteral agents (ceftriaxone, cefamandole, ceftazidime, cefotaxime) in a small number of comparative clinical trials. However, further studies are needed to clarify the comparative efficacy of ciprofloxacin with that of other oral and parenteral agents in the elderly. Initial trials have also indicated therapeutic efficacy of oral ciprofloxacin in malignant external otitis and bacterial prostatitis. Nevertheless, with its good tolerability profile and potent antimicrobial activity following oral administration, ciprofloxacin appears to offer a valuable alternative for treating various acute and chronic infections in elderly patients. Causative pathogens are frequently multiresistant in this patient group, and ciprofloxacin avoids or minimises the need for parenteral therapy.

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“…Note that there is an absorption interaction between ciprofloxacin and didanosine with cations as discussed previously [33,34]. Ciprofloxacin does not interact pharmacokinetically with metronidazole [95].…”

Section: Metabolism Interactionsmentioning

confidence: 93%

Quinolones

Guay¹

2011

Drug Interactions in Infectious Diseases

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Fluoroquinolone (FQ) antimicrobials are among the most commonly used agents in the outpatient and institutional patient care environments. Due to this high frequency of utilization, the potential for deleterious drug-drug interactions with nonantimicrobials is also high. The majority of interactions with the FQs involve deleterious effects on the FQ component. These are also the most clinically-important interactions with these agents. Multivalent cations such as Mg , and other minerals as well as drugs such as sucralfate, lanthanum, sevelamer, and didanosine (the cation-supplemented version of the latter) can substantially reduce FQ bioavailability, leading the subtherapeutic drug concentrations at the infection site and clinical failure. Separation of dose administrations may or may not reduce the magnitude of these interactions. Ciprofloxacin, norfloxacin, and two experimental FQs in clinical trials (pazufloxacin and prulifloxacin) act as moderate cytochrome P450 enzyme inhibitors and may increase serum concentrations of theophylline and caffeine. Warfarin pharmacodynamics are variably affected by the FQs. The pharmacodynamic interactions between NSAIDs and FQs are only relevant if fenbufen is used concurrently with enoxacin or, possibly, prulifloxacin. Caution is warranted if sparfloxacin or moxifloxacin is used concurrently with other medications prolonging the QTc interval or if patients have other risk factors for prolongation of the QTc interval (e.g. abnormal QTc interval pre-treatment, electrolyte abnormalities, use of starvation-liquid diets, or history of heart disease). Fluoroquinolone antimicrobials can be used effectively and safely in the vast majority of patients if the clinician remembers those few drug-drug interactions that are clinically-important.

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Metabolic interactions of ciprofloxacin

Cited by 12 publications

References 14 publications

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Clinical Pharmacokinetics of Metronidazole and Other Nitroimidazole Anti-Infectives

Ciprofloxacin

Quinolones

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