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Table 1 Currently available anti-leishmanial drugs for treatment of VL: product name, cure rate, mode of action on parasite, advantages and limitations

From: Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective

S.N.

Drugs

Marketing authotization and commercial product

Cure rate

Mechanism of action

Advantages

Limitations

1

Pentavalent antimonials

Albert David, India (generic SSG); Wellcome (Pentostam); Sanofi Aventis (Glucantime)

39–95 % depending on geographical condition (50 % in Bihar)

Act as prodrug, inhibit trypanothione reductase, increase the ROS

Low cost and easy available

Parasite resistance especially in India, cardiotoxic, 30 day iv/im treatment in hospital, painful injections

Inhibit macromolecular biosynthesis in amastigotes

2

Amphotericin B

Life care, India

>98 % in all regions

Form complexes with sterols mainly ergosterols of parasite membrane leading to increase permeability resulting in cell death

High efficacy, 1st line treatment in case of antimonial resistance

Dose-limiting renal toxicity, 15–30 day slow iv infusion treatment over 4–6h in hospital, hypokalaemia

(Fungitericin); Bristol –Myers (Fungisone)

3

Liposomal amphotericin B

Gilead (AmBisome);

>98 %

Targeted delivery of drug to infected macrophages and kill the parasites as AmB

Highest therapeutic index of available VL drugs, No need of hospitalization, substantially less nephro-toxic than AmB

Expensive, requirement of cool chain temperature maintainance

Lifecare Innovation (Fungisome); Bharat Serum and Vaccine (Amphomul);

Sequus Pharmaceuticals (Amphocil);

ENZON Pharmaceuticals (Abelcet);

Lifecare Innovation (Kalsome)

4

Miltefosine

Paladin Labs (Impavido)

94–97 %

Modulate cell surface receptors and inositol metabolism of parasites, and cell death is mediated by apoptosis, Inhibit the cytochrome C oxidase

Oral drug, Safe in HIV-VL co-infection

Teratogenic in experimental animals, originally developed as an anti- cancer drug, expensive, GI toxicity, hepato- & renaltoxicity in phase-4

5

Paromomycin

Gland Pharma/iOWH

94 % (India)

Binds to 30S ribosomal subunit and interfere with protein biosynthesis, decrease the membrane potential of parasite

Cheapest drug

An aminoglycoside, therefore nephro- and ototoxicity possible, but have not been reported in VL patients, although reversible high tone audiometric shift may occasionally occur during treatment

6

Pentamidine

Sanofi Aventis (Pentacarinat)

70–80 %

Inhibit mitochondrial topoisomerase II and inhibit the transcription process

Effective in combination therapy

Gastointestinal adverse effect, hypotension, diabetes mellitus