Uptake of chloroquine by Onchocerca volvulus in vivo and in vitro.
Patients infected with Onchocerca volvulus in the Cayapa River focus in north-east Ecuador were given 500 mg chloroquine diphosphate (CQ) orally prior to nodulectomy. The concentrations of CQ were determined in parasite fragments and host tissue dissected from the nodules, in skin overlying the nodules, and in plasma at 3, 4, 7, and 24 hours after dosing. Onchocerca volvulus took up CQ rapidly, in some cases accumulating the drug to concentrations of over 600 pmol mg-1 worm tissue by three hours, and maintaining similar concentrations through 24 hours. These amounts were markedly higher than peak concentrations in plasma (3.16 pmol microliters-1) and in host tissues (78 pmol mgm-1) and skin (up to 93 pmol mg-1). In vitro uptake of CQ by females of O. volvulus was greater under alkaline conditions (pH 8.4) than at pH 6.8 and 7.4. Uptake reached equilibrium after one to two hours, with final concentrations being approximately 10 times lower than those reached in vivo. Inhibitory effects of chloroquine and its major metabolite desethylchloroquine on the motility of O. volvulus and other filariae have been observed previously in vitro; whether or not the drug had adverse effects on adult parasites in vivo was not determined in these experiments. However, the results illustrate the accessibility of O. volvulus to blood borne agents in vivo, and the potential importance of pharmacodynamic characteristics in the search for new macrofilaricidal agents.
Mahmoud
B M
BM
NIH Sudan Medical Research Project, Alamarat, Khartoum.
Vandewaa
E A
EA
Geary
T G
TG
Guderian
R
R
Williams
J F
JF
D000818:Animals; D002738:Chloroquine / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009854:Onchocerca / Q000378:metabolism*; D009855:Onchocerciasis / Q000378:metabolism*; D013997:Time Factors
D002738:Chloroquine