Trial reportMalaria journal2007
Pharmacokinetics and pharmacodynamics of fosmidomycin monotherapy and combination therapy with clindamycin in the treatment of multidrug resistant falciparum malaria.
Trial report in Malaria journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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.
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Who cites it
25 citing papers in PubMed, 61 citations in OpenAlex.
- Population pharmacokinetics of fosmidomycin and clindamycin in combination with artesunate for uncomplicated Plasmodium falciparum malaria in Gabonese children and adults.Malaria journal · 2026Trial
- Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria.Antimicrobial agents and chemotherapy · 2012Trial
- In vitro activity of the antimalarial, antibiotic drugs fosmidomycin and clindamycin against clinical isolates of bacterial bloodstream infections in febrile, hospitalized Ghanaian children.Malaria journal · 2026Article
- Recent advances in microbially derived chlorinated antiparasitic compounds.Molecular diversity · 2025Review
- Development and application of an LC-MS/MS method for quantification of fosmidomycin in human and rat plasma.Malaria journal · 2025Article
- Host-Derived Geranylgeraniol Shields Intraerythrocytic Stages of Malaria Parasites from Fosmidomycin.Research square · 2025Article
- Article
- Design and synthesis of non-hydroxamate lipophilic inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR):RSC advances · 2024Article
- 1-Deoxy-d-xylulose 5-phosphate reductoisomerase as target for anti Toxoplasma gondii agents: crystal structure, biochemical characterization and biological evaluation of inhibitors.The Biochemical journal · 2024Article
- The Multifaceted MEP Pathway: Towards New Therapeutic Perspectives.Molecules (Basel, Switzerland) · 2023Review
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Apicoplast Journey and Its Essentiality as a Compartment for Malaria Parasite Survival.Frontiers in cellular and infection microbiology · 2022Article
- Inhibitory Effects of Fosmidomycin AgainstFrontiers in cell and developmental biology · 2020Article
- Article
- Acyloxybenzyl and Alkoxyalkyl Prodrugs of a Fosmidomycin Surrogate as Antimalarial and Antitubercular Agents.ACS medicinal chemistry letters · 2018Article
- A high-throughput screening campaign to identify inhibitors of DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD).Analytical biochemistry · 2018Article
- In silico identification of promiscuous scaffolds as potential inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase for treatment of Falciparum malaria.Pharmaceutical biology · 2017Article
- Article
- Resistance to the antimicrobial agent fosmidomycin and an FR900098 prodrug through mutations in the deoxyxylulose phosphate reductoisomerase gene (dxr).Antimicrobial agents and chemotherapy · 2015Article
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe study investigated the pharmacokinetics of fosmidomycin when given alone and in combination with clindamycin in patients with acute uncomplicated falciparum malaria.
methodsA total of 15 and 18 patients with acute uncomplicated Plasmodium falciparum malaria who fulfilled the enrollment criteria were recruited from out-patient department of Mae Sot Hospital, Tak Province, Thailand. Patients were treated with monotherapy with fosmidomycin at the dose of 1,200 mg every 8 hours for 7 days (n = 15) or combination therapy with fosmidomycin (900 mg every 12 hours for 7 days) and clindamycin (600 mg every 12 hours for 7 days) (n = 18). Blood samples were taken for pharmacokinetic investigations of clindamycin and/or fosmidomycin and 24-hour urine samples were collected during dosing period. Efficacy assessments included clinical and parasitological evaluation. Safety and tolerability were assessed based on clinical and laboratory investigations.
resultsBoth mono- and combination therapy regimens of fosmidomycin were well tolerated with no serious adverse events. Combination therapy with fosmidomycin and clindamycin was proven highly effective with 100% cure rate, whereas cure rate of monotherapy was 22% (28-day follow up). Pharmacokientics of fosmidomycin following mono- and combination therapy were similar except Vz/F and CL/F, which were significantly smaller in the combination regimen. Plasma concentration-time profiles of both fosmidomycin and clindamycin were best fit with a one-compartment open model with first-order absorption and elimination and with absorption lag time. Steady-state plasma concentrations of fosmidomycin and clindamycin were attained at about the second or third dose. There was no evidence of dose accumulation during multiple dosing. Urinary recovery of fosmidomycin was 18.7 and 20% following mono- and combination therapy, respectively.
conclusionPharmacokinetic dose optimization of fosmidomycin-clindamycin combination therapy with the course of treatment of not longer than three days is required to obtain a regimen which is safe and produced 100% cure for multidrug-resistant P. falciparum.
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