title: Onchocercacidal effect of three drug regimens of amocarzine in 148 patients of two races and both sexes from Esmeraldas, Ecuador.
abstract: The objective of this multidisciplinary clinical investigation was to test whether amocarzine was absorbed effectively and safely in patients of two races and either sex infected with Onchocerca volvulus while living in the holoendemic area of Esmeraldas Province, Ecuador. The prerequisite for a systemic onchocercacidal effect is the regular absorption of orally administered amocarzine. Single dosing after overnight fasting proved to produce irregular absorption of amocarzine, although some microfilaricidal effect was achieved. A pilot study with repeated low dose and postprandial administration of amocarzine showed a regular and predictable absorption with acceptable tolerability and a microfilaricidal effect lasting up to one year post-therapy. Since amocarzine and its major N-oxide metabolite are coloured agents, urine colorimetry was used to assess the urinary excretion of the N-oxide qualitatively. For the postprandial drug regimens plasma concentrations of amocarzine and its metabolite were determined at two selected time points in patients of two races and either sex; the results showed no major differences. Excision of onchocercal nodules was performed four months post-therapy. The pooled results of the histologic analysis of 100 patients with the same drug regimen read under blinded condition showed that 65% of the adult female worms were dead, 20% necrobiotic and 15% alive. The male worms were fewer and mainly necrobiotic. Control worm populations in Esmeraldas without chemotherapy showed that on the average 81.5% were alive and 18.5% dead. Amocarzine was also microfilaricidal producing a reduction of skin dwelling microfilariae to about 10% of the initial value within the first week after start of therapy and lasting for half a year at a 20% level. The reduction of ocular microfilarial was slower and reached 35-40% after one year. The general tolerability was acceptable to good. Reversible dermal reactions were usually mild and peaked as a rash in 57% of the patients on day 6. No prohibitive ocular intolerance was observed. Mild and reversible dizziness peaked on day 4 in 74% of patients. A positive reversible Romberg sign was found in 12 patients on day 4. Amocarzine, the first oral micro- and macrofilaricidal agent administered as a low dose repeat regimen (3 mg/kg twice daily and postprandial for three consecutive days) can be recommended for oral onchocercacidal therapy in adult patients. Clinical trials in juveniles should be encouraged.
authors.affiliation: Onchocerciasis Control Project Ministry of Health, Quito, Ecuador.
authors.forename: R H
authors.initials: RH
authors.lastname: Guderian
authors.forename: M
authors.initials: M
authors.lastname: Anselmi
authors.forename: R
authors.initials: R
authors.lastname: Proaño
authors.forename: A
authors.initials: A
authors.lastname: Naranjo
authors.forename: A A
authors.initials: AA
authors.lastname: Poltera
authors.forename: M
authors.initials: M
authors.lastname: Moran
authors.forename: J B
authors.initials: JB
authors.lastname: Lecaillon
authors.forename: F
authors.initials: F
authors.lastname: Zak
authors.forename: S
authors.initials: S
authors.lastname: Cascante
mesh_terms: D000042:Absorption; D000328:Adult; D000818:Animals; D044383:Black People; D003124:Colorimetry; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D004484:Ecuador; D005260:Female; D005369:Filaricides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007199:Indians, South American; D008297:Male; D008842:Microfilariae / Q000187:drug effects; D009854:Onchocerca / Q000187:drug effects*; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D015827:Onchocerciasis, Ocular / Q000188:drug therapy / Q000469:parasitology; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012867:Skin / Q000469:parasitology
chemical_list: D005369:Filaricides; D010879:Piperazines; C051744:amocarzine