Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis

Autor: Nancy G. Saravia, Thomas P. C. Dorlo, Adriana Navas, Maria Adelaida Gomez, Maria del Mar Castro, Eduardo Ortiz, Alexandra Cossio, Anke E. Kip
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Gastroenterology
0302 clinical medicine
Parasitic Sensitivity Tests
Pharmacology (medical)
Pharmaceutical sciences
Child
Leishmania guyanensis
biology
Middle Aged
16. Peace & justice
3. Good health
Treatment Outcome
Infectious Diseases
Area Under Curve
Child
Preschool
Female
miltefosine
pharmacokinetics
medicine.drug
Adult
medicine.medical_specialty
Adolescent
Phosphorylcholine
030106 microbiology
030231 tropical medicine
Antiprotozoal Agents
Leishmaniasis
Cutaneous
Peripheral blood mononuclear cell
Drug Administration Schedule
Leishmania braziliensis
cutaneous leishmaniasis
03 medical and health sciences
children
Pharmacokinetics
Cutaneous leishmaniasis
Internal medicine
medicine
Humans
Pharmacology
Miltefosine
business.industry
Leishmania
biology.organism_classification
medicine.disease
Clinical trial
Pharmacodynamics
Leukocytes
Mononuclear
intracellular miltefosine
business
Zdroj: Antimicrobial Agents and Chemotherapy
ISSN: 1098-6596
0066-4804
DOI: 10.1128/aac.02198-16
Popis: An open-label pharmacokinetics (PK) clinical trial was conducted to comparatively assess the PK and explore the pharmacodynamics (PD) of miltefosine in children and adults with cutaneous leishmaniasis (CL) in Colombia. Sixty patients, 30 children aged 2 to 12 years and 30 adults aged 18 to 60 years, were enrolled. Participants received miltefosine (Impavido) at a nominal dose of 2.5 mg/kg/day for 28 days. Miltefosine concentrations were measured in plasma and peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry of samples obtained during treatment and up to 6 months following completion of treatment, when therapeutic outcome was determined. Fifty-two patients were cured, 5 pediatric patients failed treatment, and 3 participants were lost to follow-up. Leishmania ( Viannia ) panamensis predominated among the strains isolated (42/46; 91%). Noncompartmental analysis demonstrated that plasma and intracellular miltefosine concentrations were, overall, lower in children than in adults. Exposure to miltefosine, estimated by area under the concentration-time curve and maximum concentration, was significantly lower in children in both the central and intracellular compartments ( P < 0.01). Leishmania persistence was detected in 43% of study participants at the end of treatment and in 27% at 90 days after initiation of treatment. Clinical response was not dependent on parasite elimination. In vitro miltefosine susceptibility was similar for Leishmania strains from adults and children. Our results document PK differences for miltefosine in children and adults with cutaneous leishmaniasis that affect drug exposure and could influence the outcome of treatment, and they provide bases for optimizing therapeutic regimens for CL in pediatric populations. (This study has been registered at ClinicalTrials.gov under identifier NCT01462500.)
Databáze: OpenAIRE
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