5-Fluorocytosine Kinetics in Patients with Acute Renal Failure Undergoing Continuous Hemofiltration

Ittel, T. H.; Legler, Udo F.; Polak, Anna; Glöckner, W. M.; Sieberth, H G

doi:10.1159/000238478

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…The causality of 5-FC-induced thrombocytopenia is strength-ened by the observation that there was a significant linear association between the thrombocyte nadir and 5-FC clearance in the group of patients who develop thrombocytopenia or remain within the normal thrombocyte range during 5-FC therapy. Also, a significant linear correlation between 5-FC clearance and creatinine clearance could be demonstrated, in accordance with the findings in other studies [18,19]. The combination of the two linear relationships results in an expression between creatinine clearance and thrombocyte nadir making it possible to predict the thrombocyte nadir from the creatinine clearance.…”

Section: Discussionsupporting

confidence: 90%

Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters

2000

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Flucytosine (5-fluorocytosine, 5-FC) is a systemic antimycotic drug the major toxicities of which are bone marrow depression and hepatotoxicity. The purpose of this observational and retrospective study was to assess a possible relationship between toxicity and 5-FC pharmacokinetics within a group of 53 intensive care unit patients. The presented results reveal that thrombocytopenia is associated with a decreased 5-FC clearance and that the thrombocyte nadir is linearly related to the 5-FC clearance. Furthermore, patients experiencing 5-FC levels exceeding 100 mg 5-FC/l were found to be at a higher risk of developing thrombocytopenia and hepatotoxicity as compared to those not exceeding this level.

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Section: Discussionsupporting

confidence: 90%

Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters

2000

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“…In earlier studies with critically ill patients, 5-FC clearance was correlated with Q uf , and T 1/2 was significantly increased with low ultrafiltration rates [61,62]. Similar findings have also been observed in two recent reports of 5-FC clearance in CVVHF and continuous venovenous haemodialysis (CVVHD) patients [63,64].…”

Section: Renal Replacement Therapysupporting

confidence: 84%

Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review

Sinnollareddy

Peake

Roberts

et al. 2012

International Journal of Antimicrobial Agents

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“…In patients with GFR <10 ml/min «0.6 L/h), the drug should be administered even less frequently and dosage should be adjusted in response to plasma drug concentrations (Daneshmend & Warnock 1983;Polak 1979). Aucytosine is removed by haemodialysis, peritoneal dialysis and continuous haemofiltration (Ittel et al 1987;Polak 1979).…”

Section: Hepatic and Renal Impairmentmentioning

confidence: 99%

Pharmacokinetic Optimisation of Oral Antifungal Therapy

Schäfer‐Korting

1993

Clinical Pharmacokinetics

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The range of oral antifungal therapy has been expanded recently by the introduction of itraconazole, and terbinafine. These agents have a broader spectrum of activity than griseofulvin and flucytosine, and induce less liver toxicity than ketoconazole. Treatment with these agents may be optimised by application of pharmacokinetic principles. Griseofulvin, ketoconazole and itraconazole should be administered with food to ensure adequate absorption. Maximal absorption of griseofulvin is achieved by administration of the drug as a solid solution in polyethylene glycol. Absorption of azole antifungal agents is impaired by high gastric pH, which is observed in some patients with acquired immunodeficiency syndrome. It is also impaired by frequent vomiting, which commonly occurs in patients with neutropenia. Furthermore, antacids, H2-antagonists and sucralfate interfere with absorption of ketoconazole. The newer oral antifungals are more slowly eliminated and associated with less pronounced drug interactions than ketoconazole. As with ketoconazole, itraconazole and fluconazole influence cyclosporin metabolism. These effects are of clinical relevance and necessitate cyclosporin dosage reduction. However, the cyclosporin dosage reduction required during coadministration of itraconazole and fluconazole (50 to 55%) is less than that required when ketoconazole is concomitantly administered (85%). Monitoring of cyclosporin concentrations during coadministration with these agents is necessary to avoid nephrotoxicity. Drug monitoring is also advisable when phenytoin, carbamazepine or rifampicin (rifampin) are administered concomitantly with azoles, due to a mutual influence on drug metabolism. The antifungal activity of itraconazole is not related exclusively to free drug concentrations. Therefore, the low protein binding of fluconazole does not place this agent at an advantage over itraconazole in the treatment of fungal meningitis. However, terbinafine may be superior to itraconazole for the treatment of tinea unguium, another recalcitrant fungal disease, because terbinafine more rapidly penetrates the nail plate. During repeated use, itraconazole concentrations increase slowly in the nail plate. Steady-state concentrations are reached in the stratum corneum only after several weeks' administration. Following cessation of treatment, terbinafine, itraconazole and ketoconazole concentrations in keratinised tissues decline slowly. This allows a short duration of drug treatment. Some clinical trials suggest that low concentrations of flucytosine, griseofulvin and itraconazole are associated with treatment failure. Flucytosine-induced myelotoxicity also appears to be concentration dependent. This adverse reaction may be caused by fluorouracil (which is produced by metabolism of flucytosine by enterobacillary flora in the gut) rather than by the parent compound.

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5-Fluorocytosine Kinetics in Patients with Acute Renal Failure Undergoing Continuous Hemofiltration

Cited by 14 publications

References 21 publications

Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters

Flucytosine: Correlation between Toxicity and Pharmacokinetic Parameters

Using pharmacokinetics and pharmacodynamics to optimise dosing of antifungal agents in critically ill patients: a systematic review

Pharmacokinetic Optimisation of Oral Antifungal Therapy

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