Efficacy, Safety, and Pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for Treatment of Bancroftian Filariasis.
BACKGROUND
Available treatments for lymphatic filariasis (LF) are limited in their longterm clearance of microfilaria from the blood. The safety and efficacy of a single-dose triple-drug therapy of the antifilarial drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) for LF are unknown.


METHODS
We performed a pilot study to test the efficacy, safety, and pharmacokinetics of single-dose DEC, IVM, and ALB in Wuchereria bancrofti-infected Papua New Guineans. Adults were randomized into 2 treatment arms, DEC 6 mg/kg + ALB 400 mg (N = 12) or DEC 6 mg/kg + ALB 400 mg + IVM 200 μg/kg (N = 12), and monitored for microfilaria, parasite antigenemia, adverse events (AEs), and serum drug levels.


RESULTS
Triple-drug therapy induced >2-log reductions in microfilaria levels at 36 and 168 hours after treatment compared with approximately 1-log reduction with 2 drugs. All 12 individuals who received 3 drugs were microfilaria negative 1 year after treatment, whereas 11 of 12 individuals in the 2-drug regimen were microfilaria positive. In 6 participants followed 2 years after treatment, those who received 3 drugs remained microfilaria negative. AEs, particularly fever, myalgias, pruritus, and proteinuria/hematuria, occurred in 83% vs 50% of those receiving triple-drug compared to 2-drug treatment respectively (P = .021); all resolved within 7 days after treatment. No serious AEs were observed in either group. There was no significant effect of IVM on DEC or ALB drug levels.


CONCLUSIONS
Triple-drug therapy is safe and more effective than DEC + ALB for Bancroftian filariasis and has the potential to accelerate elimination of lymphatic filariasis.


BACKGROUND
NCT01975441.
Papua New Guinea Institute of Medical Research, Papua New Guinea.|Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Edward K
EK
Thomsen
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Nelly
N
Sanuku
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Manasseh
M
Baea
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Samson
S
Satofan
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Elit
E
Maki
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Bart
B
Lombore
Department of Pharmaceutical Sciences & Experimental Therapeutics, University of Iowa, Iowa City.
Mark S
MS
Schmidt
Papua New Guinea Institute of Medical Research, Papua New Guinea.
Peter M
PM
Siba
Department of Medicine, Infectious Diseases Division, Washington University School of Medicine, St. Louis, Missouri.
Gary J
GJ
Weil
Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio.
James W
JW
Kazura
Department of Pharmaceutical Sciences & Experimental Therapeutics, University of Iowa, Iowa City.
Lawrence L
LL
Fleckenstein
Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, Ohio.|Veterans Affairs Medical Center, Cleveland, Ohio.
Christopher L
CL
King
D000328:Adult; D015766:Albendazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D004049:Diethylcarbamazine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D004605:Elephantiasis, Filarial / Q000188:drug therapy*; D005260:Female; D005369:Filaricides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010219:Papua New Guinea; D018512:Parasitemia / Q000188:drug therapy; D010865:Pilot Projects; D044967:Serum / Q000737:chemistry; D016037:Single-Blind Method; D016896:Treatment Outcome; D014958:Wuchereria bancrofti / Q000302:isolation & purification; D055815:Young Adult
D005369:Filaricides; D007559:Ivermectin; D015766:Albendazole; D004049:Diethylcarbamazine
albendazole; chemotherapy; diethylcarbamazine; ivermectin; lymphatic filariasis