PMID- 31107869 OWN - NLM STAT- MEDLINE DCOM- 20191025 LR - 20220716 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 13 IP - 5 DP - 2019 May TI - Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without Wuchereria bancrofti infection in Cote d'Ivoire. PG - e0007325 LID - 10.1371/journal.pntd.0007325 [doi] LID - e0007325 AB - BACKGROUND: A single co-administered dose of ivermectin (IVM) plus diethylcarbamazine (DEC) plus albendazole (ALB), or triple-drug therapy, was recently found to be more effective for clearing microfilariae (Mf) than standard DEC plus ALB currently used for mass drug administration programs for lymphatic filariasis (LF) outside of sub-Saharan Africa. Triple-drug therapy has not been previously tested in LF-uninfected individuals from Africa. This study evaluated the pharmacokinetics (PK), safety, and efficacy of triple-drug therapy in people with and without Wuchereria bancrofti infection in West Africa. METHODS: In this open-label cohort study, treatment-naive microfilaremic (>50 mf/mL, n = 32) and uninfected (circulating filarial antigen negative, n = 24) adults residing in Agboville district, Cote d'Ivoire, were treated with a single dose of IVM plus DEC plus ALB, and evaluated for adverse events (AEs) until 7 days post treatment. Drug levels were assessed by liquid chromatography and mass spectrometry. Persons responsible for assessing AEs were blinded to participants' infection status. FINDINGS: There was no difference in AUC0-inf or Cmax between LF-infected and uninfected participants (P>0.05 for all comparisons). All subjects experienced mild AEs; 28% and 25% of infected and uninfected participants experienced grade 2 AEs, respectively. There were no severe or serious adverse events. Only fever (16 of 32 versus 4 of 24, P<0.001) and scrotal pain/swelling in males (6 of 20 versus 0 of 12, P = 0.025) were more frequent in infected than uninfected participants. All LF positive participants were amicrofilaremic at 7 days post-treatment and 27 of 31 (87%) remained amicrofilaremic 12 months after treatment. CONCLUSIONS: Moderate to heavy W. bancrofti infection did not affect PK parameters for IVM, DEC or ALB following a single co-administered dose of these drugs compared to uninfected individuals. The drugs were well tolerated. This study confirmed the efficacy of the triple-drug therapy for clearing W. bancrofti Mf and has added important information to support the use of this regimen in LF elimination programs in areas of Africa without co-endemic onchocerciasis or loiasis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02845713. FAU - Edi, Constant AU - Edi C AD - Centre Suisse de Recherche Scientifique en Cote d'Ivoire, Cote d'Ivoire. FAU - Bjerum, Catherine M AU - Bjerum CM AD - Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America. FAU - Ouattara, Allassane F AU - Ouattara AF AUID- ORCID: 0000-0002-3856-8406 AD - Centre Suisse de Recherche Scientifique en Cote d'Ivoire, Cote d'Ivoire. AD - Universite Nangui Abrogoua, Cote d'Ivoire. FAU - Chhonker, Yashpal S AU - Chhonker YS AD - Dept of Pharmacy Practice, University of Nebraska Medical Center, Omaha, NE, United States of America. FAU - Penali, Louis K AU - Penali LK AD - Institut Pasteur de Cote d'Ivoire, Cote d'Ivoire. FAU - Meite, Aboulaye AU - Meite A AD - Programme National de la Lutte Contre la Schistosomiase, les Geohelminthiases et la Filariose Lymphatique, Abidjan, Cote d'Ivoire. FAU - Koudou, Benjamin G AU - Koudou BG AD - Centre Suisse de Recherche Scientifique en Cote d'Ivoire, Cote d'Ivoire. AD - Universite Nangui Abrogoua, Cote d'Ivoire. AD - Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, United Kingdom. FAU - Weil, Gary J AU - Weil GJ AD - Infectious Diseases Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America. FAU - King, Christopher L AU - King CL AUID- ORCID: 0000-0003-3873-7860 AD - Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, United States of America. AD - Veterans Affairs Research Service, Cleveland Veterans Affairs Medical Center, United States of America. FAU - Murry, Daryl J AU - Murry DJ AD - Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, United States of America. LA - eng SI - ClinicalTrials.gov/NCT02845713 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20190520 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 RN - 0 (Drug Combinations) RN - 0 (Filaricides) RN - 70288-86-7 (Ivermectin) RN - F4216019LN (Albendazole) RN - V867Q8X3ZD (Diethylcarbamazine) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Albendazole/*administration & dosage/adverse effects/pharmacokinetics MH - Animals MH - Cohort Studies MH - Cote d'Ivoire MH - Diethylcarbamazine/*administration & dosage/adverse effects/pharmacokinetics MH - Drug Combinations MH - Elephantiasis, Filarial/*drug therapy/parasitology MH - Female MH - Filaricides/*administration & dosage/adverse effects/pharmacokinetics MH - Humans MH - Ivermectin/*administration & dosage/adverse effects/pharmacokinetics MH - Male MH - Middle Aged MH - Treatment Outcome MH - Wuchereria bancrofti/*drug effects/physiology MH - Young Adult PMC - PMC6550417 COIS- The authors have declared that no competing interests exist. EDAT- 2019/05/21 06:00 MHDA- 2019/10/28 06:00 PMCR- 2019/05/20 CRDT- 2019/05/21 06:00 PHST- 2018/11/16 00:00 [received] PHST- 2019/03/23 00:00 [accepted] PHST- 2019/06/05 00:00 [revised] PHST- 2019/05/21 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] PHST- 2019/05/21 06:00 [entrez] PHST- 2019/05/20 00:00 [pmc-release] AID - PNTD-D-18-01743 [pii] AID - 10.1371/journal.pntd.0007325 [doi] PST - epublish SO - PLoS Negl Trop Dis. 2019 May 20;13(5):e0007325. doi: 10.1371/journal.pntd.0007325. eCollection 2019 May.