Endocrine Abstracts

Chloroquine (CHQ) the most frequently used drug for falciparum malaria in sub-Saharan Africa countries evokes adverse effects on glucose homeostasis and kidney function in African children. The complications can partly be ascribed to transiently high plasma CHQ concentrations following oral administration and/or malaria parasites. We have, however, reported that topical application of the pectin CHQ matrix patch releases CHQ into the bloodstream. Accordingly, the current study determined whether CHQ delivered via the transdermal route can reduce malaria parasites and ameliorate the side effects associated with oral CHQ. The method of CHQ patch production is similar to that previously reported. Oral glucose tolerance responses (OGT) to CHQ delivered orally or transdermally were monitored in groups of non-infected and Plasmodium berghei-infected male Sprague–Dawley rats following glucose load. Blood glucose concentrations were measured at 15-min intervals for the first hour and hourly thereafter for 3 h. Parasitaemia, plasma insulin, blood glucose and renal function were monitored over a 21-day period divided into pre-treatment (days 0–7), treatment (days 8–12) and post-treatment (days 13–21) in separate groups following a once off application of the CHQ patch (53 mg/kg) twice daily administration of CHQ (60 mg/kg, p.o.) during the treatment period. Transdermally delivered CHQ sustained plasma concentrations of CHQ and equally reduced P. berghei parasites by comparison with twice daily oral chloroquine. Compared with respective control groups, OGT responses of animals administered oral and transdermal CHQ were lower at all the time points that blood was sampled after the glucose load. Oral CHQ administration increased plasma insulin concentration whilst topical CHQ patch did not have any significant effect. Oral CHQ treatment was associated with increased urinary Na⁺ outputs and hyperkalaemia. The CHQ matrix patch did not influence these parameters. We conclude that the CHQ patch has the potential circumvent the adverse effects of oral CHQ.

Declaration of funding: This study was partly funded by the NRF South Africa and the University of KwaZulu-Natal, Research Division.