Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Feb;57(2):151-176.
doi: 10.1007/s40262-017-0570-0.

Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

Anke E Kip  1   2 , Jan H M Schellens  2   3 , Jos H Beijnen  1   2   3 , Thomas P C Dorlo  4   5
Affiliations
Review

Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

Anke E Kip et al. Clin Pharmacokinet. 2018 Feb.

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Funding

Thomas P.C. Dorlo was supported by the Netherlands Organisation for Scientific Research (NWO) through a personal Veni grant (Project Number 91617140).

Conflict of interest

Anke E. Kip, Jan H.M. Schellens, Jos H. Beijnen and Thomas P.C. Dorlo have no conflicts of interest that are relevant to the content of this review.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Copeland NK, Aronson NE. Leishmaniasis: treatment updates and clinical practice guidelines review. Curr Opin Infect Dis. 2015;28:426–437. doi: 10.1097/QCO.0000000000000194. - DOI - PubMed
    1. WHO. Control of the leishmaniases. WHO Technical Report Series #949. 2010. http://apps.who.int/iris/bitstream/10665/44412/1/WHO_TRS_949_eng.pdf. Accessed 7 Feb 2017.
    1. Croft SL, Olliaro P. Leishmaniasis chemotherapy—challenges and opportunities. Clin Microbiol Infect. 2011;17:1478–1483. doi: 10.1111/j.1469-0691.2011.03630.x. - DOI - PubMed
    1. Sundar S, Singh A. Recent developments and future prospects in the treatment of visceral leishmaniasis. Ther Adv Infect Dis. 2016;3:98–109. doi: 10.1177/2049936116646063. - DOI - PMC - PubMed
    1. Monge-Maillo B, López-Vélez R. Miltefosine for visceral and cutaneous leishmaniasis: drug characteristics and evidence-based treatment recommendations. Clin Infect Dis. 2015;60:1398–1404. - PubMed

Substances

LinkOut - more resources