Efficacy of picroliv in combination with miltefosine, an orally effective antileishmanial drug against experimental visceral leishmaniasis.
Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the major public health problems in many tropical countries. However, no effective treatment for radical cure of the disease is yet available. Miltefosine, an alkyl phospholipid compound, is the first orally effective drug, which has shown 98% cure rate of VL patients during phase III clinical trial in India. Since this drug requires long course of treatment and has long half-life, there are fairly good chances of emergence of resistance. Furthermore, this drug has produced severe side-effects in some of the cases. We therefore examined the possibility of minimizing these effects by applying miltefosine in lower doses in combination with picrloviv, an immunomodulator against Leishmania donovani in hamsters (Mesocricetus auratus). The picroliv per se showed no antileishmanaial potential. However, when given with suboptimal dose of miltefosine, it enhanced efficacy of the latter from 45 to 86% on day 7 post treatment and from 32 to 64% on day 28 post treatment. Interestingly, the efficacy of this combination was as good as the curative dose of miltefosine alone. Thus, this combination appears to offer a fruitful strategy for treatment of VL.
Gupta
Suman
S
Divisions of Parasitology, Central Drug Research Institute, Lucknow 226001, India. gupta_suman@yahoo.com
Ramesh
S C Sharma
SC
Srivastava
V M L
VM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000494:pharmacology*; D001706:Biopsy; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D006224:Cricetinae; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D007893:Leishmania donovani / Q000254:growth & development*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D032261:Picrorhiza / Q000737:chemistry; D014641:Vanillic Acid / Q000302:isolation & purification / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000981:Antiprotozoal Agents; D002934:Cinnamates; D006027:Glycosides; D010767:Phosphorylcholine; C057463:kutkin; C039128:miltefosine; D014641:Vanillic Acid