Clinical Pharmacokinetics

, Volume 21, Issue 6, pp 479–493 | Cite as

Pharmacokinetic Justification of Antiprotozoal Therapy

A US Perspective
  • Jonathan D. Berman
  • Lawrence Fleckenstein
Review Article Pharmacokinetics-Therapeutics


Infections with parasitic protozoa have always been problems for the developing world and are becoming of greater importance to the developed world in this age of easy international travel. The major human protozoal diseases are summarised with an emphasis on their presentation in normal hosts and in immunocompromised individuals and current US drug treatment recommendations are discussed. Present antiprotozoal regimens are based either on a pharmacokinetic rationale or on clinical trial and error. Regimens based on trial and error include amphotericin B against leishmaniasis and arsenic against African trypanosomiasis. Regimens which are to some extent driven by pharmacokinetic or biochemical considerations include paromomycin and metronidazole against amoebiasis, sodium stibogluconate against leishmaniasis, halofantrine and mefloquine against malaria, dihydrofolate reductase (DHFR) inhibitors against Pneumocystis carinii and toxoplasmosis and aerosolised pentamidine against P. carinii pneumonia. The majority of pharmacokinetic studies have been performed only on agents which have some therapeutic activity against other diseases of the developed world. Despite the trend toward rational treatment regimens, no studies have been performed that permit optimisation of antiprotozoal treatment regimens on the basis of clinical conditions such as renal failure.


Malaria Mefloquine Visceral Leishmaniasis Leishmaniasis Toxoplasmosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abramowicz M (Ed.) Drugs for parasitic infections. Medical Letter on Drugs and Therapeutics 30: 15–24, 1988Google Scholar
  2. Allegra CJ, Kovacs JA, Drake JC, Swan JC, Chabner BA, et al. Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent. Journal of Experimental Medicine 165: 926–931, 1987aPubMedCrossRefGoogle Scholar
  3. Allegra CJ, Kovacs JA, Drake JC, Swan JC, Chabner BA, et al. Potent in vitro and in vivo antitoxoplasma activity of the lipid soluble antifoiate trimetrexate. Journal of Clinical Investigation 79: 478–482, 1987bPubMedCrossRefGoogle Scholar
  4. Boudreau E, Fleckenstein L, Pang LW, Childs GE, Schroeder AC, et al. Mefloquine kinetics in cured and recrudescent patients with acute falciparim malaria and in healthy volunteers. Clinical Pharmacology and Therapeutics 48: 349–409, 1990Google Scholar
  5. Breckenridge A, Back DJ, Edwards IG, Mihaly G, Orne M, et al. The clinical and biochemical pharmacology of primaquine. In Wernsdorfer & Trigg (Eds) Primaquine: pharmacokinetics, metabolism, toxicity and activity, pp. 65–75, Wiley and Sons, New York, 1987Google Scholar
  6. Bushby SRM, Hitchings GH. Trimethoprim, a sulfonamide potentiator. British Journal of Pharmacology and Chemotherapy 33: 72–90, 1968PubMedGoogle Scholar
  7. Christiansen KJ, Bernard EM, Gold J, Armstrong D. Distribution and activity of amphotericin B in humans. Journal of Infectious Diseases 152: 1037–1043, 1985PubMedCrossRefGoogle Scholar
  8. Chulay JD, Fleckenstein L, Smith DH. Pharmacokinetics of antimony during treatment of visceral leishmaniasis with sodium stibogluconate or meglumine antimoniate. Transactions of the Royal Society of Tropical Medicine and Hygiene 82: 69–72, 1988PubMedCrossRefGoogle Scholar
  9. Collins JM, Klecker RW, Yarchoan R, Lane HC, Fauci AS, et al. Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection. Journal of Clinical of Pharmacology 26: 22–26, 1986Google Scholar
  10. Conte JE, Golden JA. Concentrations of aerosolised pentamidine in bronchoalveolar lavage, systemic absorption and excretion. Antimicrobial Agents and Chemotherapy 32: 1490–1493, 1988PubMedCrossRefGoogle Scholar
  11. Davey RT, Masur H. Recent advances in the diagnosis, treatment and prevention of Pneumocystis carinii pneumonia. Antimicrobial Agents and Chemotherapy 34: 499–504, 1990PubMedCrossRefGoogle Scholar
  12. Donnelly H, Bernard EM, Rothkotter H, Gold J, Armstrong D. Distribution of pentamidine in patients with AIDS. Journal of Infectious Diseases 157: 985–990, 1988PubMedCrossRefGoogle Scholar
  13. Editorial. Recommendations for the prevention of malaria among travellers. Morbidity and Mortality Weekly Report 39: 1–10, 1990Google Scholar
  14. Editorial. Treatment of severe Plasmodium falciparum malaria with quinidine gluconate: discontinuation of parenteral quinine from CDC drug service. Morbidity and Mortality Weekly Report 40: 240, 1991Google Scholar
  15. Gallis HA, Drew RH, Pickard WW. Amphotericin B: 30 years of clinical experience. Reviews of Infectious Diseases 12: 308–328, 1990PubMedCrossRefGoogle Scholar
  16. Goodman AG, Goodman LS, Rall TW, Murad F (Eds). The pharmacological basis of therapeutics, 7th ed., Macmillan Publishing Company, New York, 1985Google Scholar
  17. Haegele KD, Alken RG, Grove J, Schecter PJ, Kockweser J. Kinetics of a-difluoromethylornithine: an irreversible inhibitor of ornithine decarboxylase. Clinical Pharmacology and Therapeutics 30: 210–217, 1991Google Scholar
  18. Jensen JC, Gugler R. Single and multiple dose metronidazole kinetics. Clinical Pharmacology and Therapeutics 34: 481–486, 1983PubMedCrossRefGoogle Scholar
  19. Karbwarg J, White NJ. Clinical pharmacokinetics of mefloquine. Clinical Pharmacokinetics 19: 264–279, 1990CrossRefGoogle Scholar
  20. Kelly JA, Fletcher KA, Chiluba EM. The kinetics of proguanil during prophylaxis. Transactions of the Royal Society of Tropical Medicine and Hygiene 80: 338, 1986Google Scholar
  21. Kovacs JA, Allegra CJ, Beaver J, Boarman D, Lewis M, et al. Characterization of de novo folate synthesis in Pneumocystis carinii and Toxoplasma gondii: potential for screening therapeutic agents. Journal of Infectious Diseases 160: 312–320, 1989PubMedCrossRefGoogle Scholar
  22. Kovacs JA, Allegra CJ, Swan JC, Drake JC, Parrilo JE, et al. Potent antipneumocystis and antitoxoplasma activities of piritrexim, a lipid-soluble antifolate. Antimicrobial Agents and Chemotherapy 32: 430–433, 1988PubMedCrossRefGoogle Scholar
  23. Lobel HO, Bernard KW, Williams SL, Hightower AW, Patchen LC, et al. Effectiveness and tolerance of long-term malaria prophylaxis with mefloquine. Journal of the American Medical Association 265: 361–364, 1991PubMedCrossRefGoogle Scholar
  24. Medenwald H, Brandau K, Schlossman K. Quantitative determination of nifurtimox in body fluids of rat, dog, and man. Arzneimittel-Forschung 22: 1613–1616, 1972PubMedGoogle Scholar
  25. Milton KA, Edwards G, Ward SA, Orme ML, Breckenridge AM. Pharmacokinetics of halofantrine in man: effects of food and dose size. British Journal of Clinical Pharmacokinetics 28: 70–77, 1989CrossRefGoogle Scholar
  26. Panisko DM, Keystone JS. Treatment of malaria — 1990. Drugs 39: 160–189, 1990PubMedCrossRefGoogle Scholar
  27. Rees PH, Keating MI, Kager PA, Hockmeyer WT. Renal clearance of pentavalent antimony (sodium stibogluconate). Lancet 2: 226–229, 1980PubMedCrossRefGoogle Scholar
  28. Shannon JA, Earle DP, Brodie BB, Taggart JV, Berliner RW. The pharmacological basis for the rational use of atabrine in the treatment of malaria. Journal of Pharmacology and Experimental Therapeutics 81: 307–330, 1944Google Scholar
  29. Soo Hoo GW, Mohsenifar Z, Meyer RD. Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia in AIDS. Annals of Internal Medicine 113: 195–202, 1990PubMedGoogle Scholar
  30. Van Nieuwenhove S, Schechter PJ, Declercq J, Bone G, Burke J, et al. Treatment of gambiense sleeping sickness in the Sudan with oral DFMO, an inhibitor of ornithine decarboxylase: first field trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 79: 692–698, 1985PubMedCrossRefGoogle Scholar
  31. Wellde BT, Chumo DA, Reardon MJ, Abinya A, Wanyama L, et al. Treatment of Rhodesian sleeping sickness in Kenya. Annals of Tropical Medicine and Parasitology 83 (Suppl. 1): 99–109, 1989PubMedGoogle Scholar
  32. Winstanley PA, Simooya O, Kofi-Ekue JM, Walker O, Salako LA, et al. The disposition of amodiaquine in Zambians and Nigerians with malaria. British Journal of Clinical Pharmacology 29: 695–701, 1990PubMedCrossRefGoogle Scholar
  33. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clinical Pharmacokinetics 10: 187–215, 1985PubMedCrossRefGoogle Scholar
  34. Wooding-Scott RA, Smalley J, Visco J, Slaughter RL. The pharmacokinetics and pharmacodynamics of quinidine and 3-hydroxyquinidine. British Journal of Clinical Pharmacology 26: 415–421, 1988PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1991

Authors and Affiliations

  • Jonathan D. Berman
    • 1
  • Lawrence Fleckenstein
    • 1
  1. 1.Walter Reed Army Institute of ResearchWashington, DCUSA

Personalised recommendations