Trial reportAntimicrobial agents and chemotherapy2006
Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers.
Trial report in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Too Much of a Good Thing: Defining Antimicrobial Therapeutic Targets to Minimize Toxicity.Clinical pharmacology and therapeutics · 2021Pooled it
- Variability and exposure-response relationships of isavuconazole plasma concentrations in the Phase 3 SECURE trial of patients with invasive mould diseases.The Journal of antimicrobial chemotherapy · 2019Trial
- Impact of Mucositis on Absorption and Systemic Drug Exposure of Isavuconazole.Antimicrobial agents and chemotherapy · 2017Trial
- Drug disposition before and after gastric bypass: fenofibrate and posaconazole.British journal of clinical pharmacology · 2016Trial
- Population Pharmacokinetics of Isavuconazole from Phase 1 and Phase 3 (SECURE) Trials in Adults and Target Attainment in Patients with Invasive Infections Due to Aspergillus and Other Filamentous Fungi.Antimicrobial agents and chemotherapy · 2016Trial
- Safety and pharmacokinetics of isavuconazole as antifungal prophylaxis in acute myeloid leukemia patients with neutropenia: results of a phase 2, dose escalation study.Antimicrobial agents and chemotherapy · 2015Trial
- Effect of mild and moderate liver disease on the pharmacokinetics of isavuconazole after intravenous and oral administration of a single dose of the prodrug BAL8557.Antimicrobial agents and chemotherapy · 2009Trial
- Central Nervous System Aspergillosis: Advances in Diagnosis, Therapeutics, and Multidisciplinary Management (2026 Update).Mycoses · 2026Review
- Pharmacokinetics of isavuconazonium sulfate and its active metabolite isavuconazole in healthy dogs.PloS one · 2024Article
- Physicochemical Characteristics of Antimicrobials and Practical Recommendations for Intravenous Administration: A Systematic Review.Antibiotics (Basel, Switzerland) · 2023Review
- Isavuconazole Exposure in Critically Ill Patients Treated with Extracorporeal Membrane Oxygenation: Two Case Reports and a Narrative Literature Review.Antibiotics (Basel, Switzerland) · 2023Article
- A physiologically based pharmacokinetic analysis to predict the pharmacokinetics of intravenous isavuconazole in patients with or without hepatic impairment.Antimicrobial agents and chemotherapy · 2023Article
- Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.Journal of fungi (Basel, Switzerland) · 2023Article
- Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses.Journal of fungi (Basel, Switzerland) · 2023Article
- Population Pharmacokinetics of Isavuconazole in Adult: A Systematic Review.Infection and drug resistance · 2023Review
- Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring.Journal of clinical medicine · 2022Article
- Isavuconazole for COVID-19-Associated Invasive Mold Infections.Journal of fungi (Basel, Switzerland) · 2022Review
- Population Pharmacokinetics and Pharmacodynamic Target Attainment of Isavuconazole againstPharmaceutics · 2021Article
- The Overview on the Pharmacokinetic and Pharmacodynamic Interactions of Triazoles.Pharmaceutics · 2021Review
- Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance.Journal of fungi (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BAL8557 is the water-soluble prodrug of BAL4815, a new broad-spectrum antifungal. Healthy male subjects were randomly assigned to four treatment cohorts to receive multiple oral doses or multiple 1-h constant-rate intravenous infusions of BAL8557. Loading doses of BAL8557 were equivalent to 100 mg (followed by once-daily maintenance doses of 50 mg) or 200 mg (followed by once-daily maintenance doses of 100 mg) of BAL4815. In each cohort, six subjects received active drug and two subjects received the placebo. Study duration was 21 days (oral) and 14 days (intravenous). All adverse events reported were mild or moderate, except one severe rhinitis event which was not related to trial medication. After both routes of administration, maximum drug concentration observed in plasma (C(max)) and area under the concentration-time curve (AUC) values of BAL4815 increased proportionally to the administered dose. AUC values reflected a fourfold to fivefold accumulation of active drug in plasma during once-daily dosing, which is in line with the long elimination half-life of BAL4815 determined after the last administration (mean, 84.5 to 117 h). At steady state, the volume of distribution was large and amounted to 308 to 542 liters. Systemic clearance reached only 2.4 to 4.1 liter/h. At the levels obtained in the present study, C(max) values of 2.56 and 2.55 microg/ml after oral and intravenous administrations, respectively, there was no indication of CYP3A4 induction or inhibition (as revealed by the urinary 6-beta-hydroxycortisol/cortisol test). Based on AUC values after oral and intravenous administration, an excellent oral bioavailability can be predicted for BAL4815. Once-daily oral dosing of 50- or 100-mg equivalents of BAL8557 were recently demonstrated to be efficacious in a phase 2 study conducted with patients with esophageal candidiasis. These doses (preceded by adequate loading dose[s]) will be further explored in the treatment of systemic mycoses.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.