Amphotericin B for Visceral Leishmaniasis in Hemodialysis

Hernandez, Estebes; Oliet, Aniana; Gallar, Paloma; Llanos, Marta; Guerra, Larissa Pereira; Vigil, Ana

doi:10.1159/000186666

Cited by 2 publications

(3 citation statements)

References 3 publications

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“…For D-AMB, ~20% of the administered dose is renally excreted within 1 week. No pharmacokinetic parameters have been defined for patients with renal impairment, but a dose of D-AMB 1 mg/kg was well-tolerated in a VL patient on haemodialysis [ 125 ]. No AMB could be identified in peritoneal dialysate [ 126 ], as expected due to high AMB protein binding.…”

Section: Specific Patient Populationsmentioning

confidence: 99%

Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

et al. 2017

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This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug–drug interactions. This overview provides an understanding of their clinical pharmacokinetics, which could assist in rationalising and optimising treatment regimens, especially in combining multiple antileishmanial drugs in an attempt to increase efficacy and shorten treatment duration. Pentavalent antimony pharmacokinetics are characterised by rapid renal excretion of unchanged drug and a long terminal half-life, potentially due to intracellular conversion to trivalent antimony. Pentamidine is the only antileishmanial drug metabolised by cytochrome P450 enzymes. Paromomycin is excreted by the kidneys unchanged and is eliminated fastest of all antileishmanial drugs. Miltefosine pharmacokinetics are characterized by a long terminal half-life and extensive accumulation during treatment. AMB pharmacokinetics differ per drug formulation, with a fast renal and faecal excretion of AMB deoxylate but a much slower clearance of liposomal AMB resulting in an approximately ten-fold higher exposure. AMB and pentamidine pharmacokinetics have never been evaluated in leishmaniasis patients. Studies linking exposure to effect would be required to define target exposure levels in dose optimisation but have only been performed for miltefosine. Limited research has been conducted on exposure at the drug’s site of action, such as skin exposure in cutaneous leishmaniasis patients after systemic administration. Pharmacokinetic data on special patient populations such as HIV co-infected patients are mostly lacking. More research in these areas will help improve clinical outcomes by informed dosing and combination of drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-017-0570-0) contains supplementary material, which is available to authorized users.

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Section: Specific Patient Populationsmentioning

confidence: 99%

Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

et al. 2017

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“…This is the first case of visceral leishmaniasis complicating mycobacterial tuberculosis infection in a haemodialysis patient and, to the best of our knowledge, only one case of visceral leishmaniasis in a haemodialysis patient has been reported [13]. It has been suggested that impaired cell-mediated immunity and inhibition of macrophage function, which are important in the elimination of intracellular microorganisms, may be predisposing factors for this kind of infection.…”

Section: Discussionmentioning

confidence: 80%

“…It has been suggested that impaired cell-mediated immunity and inhibition of macrophage function, which are important in the elimination of intracellular microorganisms, may be predisposing factors for this kind of infection. The most common underlying diseases in immunocompromised hosts with visceral leishmaniasis are haematological malignancies, renal transplantation, systemic lupus erythematosus, and HIV infection [3][4][5][6][7][8][9][10][11][12][13]. There is a tendency for a relapse of infection to occur in these patients and treatment has to be continued for several weeks or months to sterilize the infected tissues or to prevent relapse [6,11].…”

Section: Discussionmentioning

confidence: 99%