Caspofungin

Keating, Gillian M.; Jarvis, Blair

doi:10.2165/00003495-200161080-00007

Cited by 88 publications

(65 citation statements)

References 19 publications

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“…In accordance with published data (21,(23)(24)(25)(26)(27)(28), the present PopPK analysis demonstrates that no dose adjustments of CAS are necessary on the basis of gender, age, or renal impairment as assessed by the creatinine clearance. As hepatic dysfunction impacts CL for adult patients with moderate hepatic impairment (ChildPugh score, 7 to 9), adjustment of the CAS dose on the basis of PK data is recommended (23,(27)(28)(29)(30).…”

Section: Discussionsupporting

confidence: 87%

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Würthwein

Cornely

Trame

et al. 2013

Antimicrob Agents Chemother

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g Caspofungin (CAS) is approved for second-line management of proven or probable invasive aspergillosis at a dose of 50 mg once daily (QD). Preclinical and limited clinical data support the concept of the dose-dependent antifungal efficacy of CAS with preservation of its favorable safety profile. Little is known, however, about the pharmacokinetics (PKs) of higher doses of CAS in patients. In a formal multicenter phase II dose-escalation study, CAS was administered as a 2-h infusion at doses ranging from 70 to 200 mg QD. CAS PK sampling (n ‫؍‬ 468 samples) was performed on day 1 and at peak and trough time points on days 4, 7, 14, and 28 (70 mg, n ‫؍‬ 9 patients; 100 mg, n ‫؍‬ 8 patients; 150 mg, n ‫؍‬ 9 patients; 200 mg, n ‫؍‬ 20 patients; total, n ‫؍‬ 46 patients). Drug concentrations in plasma were measured by liquid chromatography tandem mass spectroscopy. Population pharmacokinetic analysis (PopPK) was performed using NONMEM (version 7) software. Model evaluation was performed using bootstrap analysis, prediction-corrected visual predictive check (pcVPC), as well as standardized visual predictive check (SVPC). The four investigated dose levels showed no difference in log-transformed dose-normalized trough levels of CAS (analysis of variance).

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Section: Discussionsupporting

confidence: 87%

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Würthwein

Cornely

Trame

et al. 2013

Antimicrob Agents Chemother

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“…However, caspofungin is not active against Cryptococcus neoformans, Trichosporon spp., or Fusarium spp. (5,11). Its apparently low toxicity and lack of known drug interactions make caspofungin an attractive parenteral alternative to more traditional forms of antifungal prophylaxis.…”

mentioning

confidence: 99%

Open-Label, Randomized Comparison of Itraconazole versus Caspofungin for Prophylaxis in Patients with Hematologic Malignancies

Mattiuzzi¹,

Alvarado²,

Giles³

et al. 2006

Antimicrob Agents Chemother

154

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. Two patients in the itraconazole group and four in the caspofungin group died of fungal infection (P ‫؍‬ 0.57). Grade 3 to 4 adverse event rates were comparable between groups; the most common event in both was reversible hyperbilirubinemia. No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60. In conclusion, intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy, and both drugs were well tolerated.

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“…Caspofungin acetate (Cancidas, formerly MK-0991 and L-743872; Merck & Co., Inc.) is an echinocandin-class antifungal agent, recently approved in the United States and Europe for the treatment of invasive aspergillosis that is refractory to other antifungal treatments, esophageal Candida infections and invasive Candida infections (11). Caspofungin inhibits synthesis of ␤-1,3-D-glucan in fungal cell walls, a property that results in fungicidal effects against Candida species, in which this polysaccharide is vital to cell wall integrity (8).…”

mentioning

confidence: 99%

Interlaboratory Comparison of Results of Susceptibility Testing with Caspofungin against Candida and Aspergillus Species

et al. 2004

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Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC 2 ) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode ؎ one dilution range across all 17 laboratories. MIC 2 at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.

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Caspofungin

Cited by 88 publications

References 19 publications

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Population Pharmacokinetics of Escalating Doses of Caspofungin in a Phase II Study of Patients with Invasive Aspergillosis

Open-Label, Randomized Comparison of Itraconazole versus Caspofungin for Prophylaxis in Patients with Hematologic Malignancies

Interlaboratory Comparison of Results of Susceptibility Testing with Caspofungin against Candida and Aspergillus Species

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