title: The entry of ivermectin and suramin into Onchocerca ochengi nodules.
abstract: No currently available drug, which is safe for mass treatment, effectively kills adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of both of these filarial nematodes are found in well developed nodules, the lack of efficacy of these drugs may be a result of their poor penetration into the nodules. To check if this was the problem, the distributions of the microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma, skin, nodule capsules and nodule contents were determined in cattle naturally infected with O. ochengi in Cameroon. The cattle were treated with either a single, subcutaneous injection of 500 micrograms ivermectin/kg, or with intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a day for 6 days. Concentrations of ivermectin and suramin in various tissues were then assayed by high-pressure liquid chromatography and scintillation counting, respectively. On day 7 post-treatment (pt), suramin concentrations were consistently highest in the nodule, contents and capsule wall (11.0 and 8.9 nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4 nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was similar, with the highest concentrations in the capsule wall, nodule contents and plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the concentration in the skin (6.4 ng/g) significantly lower than those in the capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs were maintained for 5-7 days at least and those of ivermectin would be expected to kill nematodes other than filariae. It is apparent that failure of ivermectin and suramin to kill adult Onchocerca spp. is not because the drugs penetrate nodules inadequately.
authors.affiliation: Liverpool School of Tropical Medicine, U.K. h.f.cross@liv.ac.uk
authors.forename: H F
authors.initials: HF
authors.lastname: Cross
authors.forename: B M
authors.initials: BM
authors.lastname: Bronsvoort
authors.forename: G
authors.initials: G
authors.lastname: Wahl
authors.forename: A
authors.initials: A
authors.lastname: Renz
authors.forename: D
authors.initials: D
authors.lastname: Achu-Kwi
authors.forename: A J
authors.initials: AJ
authors.lastname: Trees
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005369:Filaricides / Q000493:pharmacokinetics*; D007559:Ivermectin / Q000493:pharmacokinetics*; D009855:Onchocerciasis / Q000188:drug therapy / Q000378:metabolism / Q000662:veterinary*; D013498:Suramin / Q000493:pharmacokinetics*
chemical_list: D005369:Filaricides; D013498:Suramin; D007559:Ivermectin