Skip to main content
SpringerLink
Log in

Clinical Trials — Phases I and II

  • Chapter
Antimalarial Drugs I

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 68 / 1))

Abstract

The need for developing new antimalarials has been expressed on various occasions by the World Health Organization (WHO). The “Special Programme for Research and Training in Tropical Diseases” (TDR), established in 1975 under the auspices of the UNDP, World Bank and WHO (1980), has stimulated new efforts in this field. The highest priority has been given to the development of new antimalarials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahmad RA, Rogers HJ (1981) Salivary elimination of pyrimethamine. Br J Clin Pharmacol 11:101–102

    PubMed  CAS  Google Scholar 

  • Alving AS, Coggeshall LT (1974) Clinical testing of antimalarial drugs at Stateville Penitentiary, Malaria report 30. National Institute of Health, Washington

    Google Scholar 

  • Ambroise-Thomas P (1974) La réaction d’immunofluorescence dans l’étude séro-immuno-logique du paludisme. Bull WHO 50:267–276

    PubMed  CAS  Google Scholar 

  • Arnold JD, Martin DC, Carson PE, Rieckmann KH, Willerson D Jr, Clyde DF, Miller RM (1973) A phenanthrene methanol (WR 33063) for treatment of acute malaria. Antimicrob Agents Chemother 3:207–213

    PubMed  CAS  Google Scholar 

  • Aronsson L, Bengtsson E, Björkan A, Pehrson PO, Rombo L, Wahlgren M (1981) Chloro-quine-resistant falciparum malaria in Madagascar and Kenya. Ann Trop Med Parasitol 75:367–373

    PubMed  CAS  Google Scholar 

  • Ballif-Negulici E, Constantinesco P (1963) Therapeutic effects of a single dose of pyrimethamine in malaria inoculation with local or imported strains of P. vivax and P. falciparum. Arch Roum Pathol Exp Microbiol 22:997–1002

    PubMed  CAS  Google Scholar 

  • Berliner RW, Earle P Jr, Taggart JV et al. (1948) Studies on the chemotherapy of the human malarias VI. The physiological disposition, antimalarial activity, and toxicity of several derivatives of 4-aminoquinoline. J Clin Invest 27:98–107

    Article  CAS  Google Scholar 

  • Black RH, Dew BB, Hennessy WB, McMillan B, Torpy DC (1966) Studies on depot antimalarials: I. The effect of a single injection of the depot antimalarial CI-501 (Camolar) on relapsing vivax malaria acquired in New Guinea. Med J Aust 2:588–592

    PubMed  CAS  Google Scholar 

  • Blackwell B, Stolley PD, Buncher R, Klimt CR, Temple R, Venn D, Wardell WM (1975) Panel 4: Phase IV investigations. Clin Pharmacol Ther 18:653–656

    PubMed  CAS  Google Scholar 

  • Brohult J, Rombo L, Sirleaf V, Bengtsson E (1979) The concentration of chloroquine in serum during short- and long-term malaria prophylaxis with standard and “double” dosage in non-immunes: clinical implications. Ann Trop Med Parasitol 73:401–405

    PubMed  CAS  Google Scholar 

  • Bruce-Chwatt LJ (1967) Clinical trials of antimalarial drugs. Trans R Soc Trop Med Hyg 61:412–426

    Article  Google Scholar 

  • Canfield CJ, Hall AP, MacDonald BS, Neumann DA, Shaw JA (1973) Treatment of falciparum malaria from Vietnam with a phenanthrene methanol (WR 33063) and a quinoline methanol (WR 30090). Antimicrob Agents Chemother 3:224–227

    PubMed  CAS  Google Scholar 

  • Canfield CR, Rozman RS (1974) Clinical testing of new antimalarial compounds. Bull WHO 50:203–212

    PubMed  CAS  Google Scholar 

  • Chaput de Saintonge DM (1978) Klinische Prüfungen — leichter gesagt als getan. Internist (Berlin) 19:349–356

    CAS  Google Scholar 

  • Chin W, Contacos PG, Coatney GR, Kimball HR (1965) A naturally acquired quotidian-type malaria in man transferable to monkeys. Science 149:865

    Article  PubMed  CAS  Google Scholar 

  • Chin W, Rattanartihikul M (1973) The evaluation of the presumptive and radical treatments against falciparum malaria in Thailand. Southeast Asian J Trop Med Public Health 4:400–406

    PubMed  CAS  Google Scholar 

  • Clyde DF, Miller RM, DuPont HL, Hornick RB (1971) Antimalarial effects of tetracyclines in man. J Trop Med Hyg 74:238–242

    PubMed  CAS  Google Scholar 

  • Clyde DF, McCarthy VC, Miller RM, Hornick RB (1973) Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci 266:398–403

    Article  PubMed  CAS  Google Scholar 

  • Clyde DF, McCarthy VC, Miller RM, Woodward WE (1975) Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg 4:397–401

    Google Scholar 

  • Contacos PG, Coatney GR, Lunn JS, Kilpatrick JW (1964) The antimalarial activity of CI-501 (Camolar) against falciparum malaria. Am J Trop Med Hyg 13:386–390

    PubMed  CAS  Google Scholar 

  • Covell G, Coatney GR, Field JW, Singh I (1956) La chimiothérapie du paludisme. Monograph Series WHO 27:1–132

    Google Scholar 

  • Degơin RL, Eppes RB, Carson PE, Powell RD (1966) The effects of diaphenyl-sulfone (DDS) against chloroquine-resistant Plasmodium falciparum. Bull WHO 34:671–681

    Google Scholar 

  • Desjardins RE, Pamplin CL, Von Bredow J, Barry KG, Canfield CJ (1979) Kinetics of a new antimalarial, mefloquine. Clin Pharmacol Ther 26:372–379

    PubMed  CAS  Google Scholar 

  • Draper CC (1971) Laboratory diagnosis. Br Med J 2:93–95

    Article  PubMed  CAS  Google Scholar 

  • Ebisawa I, Komoriya T, Kimura M, Muto T (1974) Morphological and clinical effects of pyrimethamine-sulfonamide combinations (sulformethoxine-pyrimethamine or sulfa-monomethoxine-pyrimethamine) on P. vivax and its infection. Jpn J Exp Med 44:151–163

    PubMed  CAS  Google Scholar 

  • Food and Drug Administration (1977 a) General considerations for the clinical evaluation of drugs. US Department of Health, Education and Welfare, Washington, DC

    Google Scholar 

  • Food and Drug Administration (1977 b) Guidelines for the clinical evaluation of anti-infective drugs (systemic adults and children) US Department of Health, Education and Welfare, Washington, DC

    Google Scholar 

  • Food and Drug Administration (1977 c) General considerations for the clinical evaluation of drugs in infants and children. US Department of Health, Education and Welfare, Washington, DC

    Google Scholar 

  • George CF (1974) The investigation of new drugs in man. Br J Hosp Med 780–787

    Google Scholar 

  • Gerberg EJ (1971) Evaluation of antimalarial compounds in mosquito test systems. Trans R Soc Trop Med Hyg 65:358–363

    Article  PubMed  CAS  Google Scholar 

  • Gilles HM, Clyde DF (1974) Acetylator phenotype in sulphonamide-resistant falciparum malaria. Ann Trop Med Parasitol 68:367–368

    PubMed  CAS  Google Scholar 

  • Goldberg LI, Besselaar GH, Arnold JD, Lemberger L, Mitchell JR, Whitset TL (1975) Panel 1: Phase I investigations. Clin Pharmacol Ther 18:643–646

    PubMed  CAS  Google Scholar 

  • Grin EI, Pirnat L, Dimitrijevic E, Simic L (1973) Thromboangiitis and results obtained by pyretotherapy using malaria. Excerpta Medica, Public Health Social Medicine and Hygiene 21:1–53

    Google Scholar 

  • Hall AP, Doberstyn EB, Nanakorn A, Sonkom A (1975 a) Falciparum malaria semi-resistant to clindamycin. Br Med J 2:12–14

    Article  PubMed  CAS  Google Scholar 

  • Hall AP, Doberstyn EB, Mettaprakong V, Sonkom P (1975 b) Falciparum malaria cured by quinine followed by sulfadoxine-pyrimethamine. Br Med J 2:15–17

    Article  PubMed  CAS  Google Scholar 

  • Haskins WT (1958) A simple qualitative test for chloroquine in urine. Am J Trop Med 7:199–222

    CAS  Google Scholar 

  • Hickman RL (1969) The use of subhuman primates for experimental studies of human malaria. Milit Med 134:741–756

    CAS  Google Scholar 

  • Jauch R, Griesser E, Oesterhelt G (1980) Metabolismus von Ro 21–5998 (Mefloquin) bei der Ratte. Arzneimittelforsch 30:60–67

    PubMed  CAS  Google Scholar 

  • Jusko WJ (1981) Smoking and drug response. Trends Pharm Int 2:10–13

    CAS  Google Scholar 

  • Kahl GF (1978) Interaktionen von Arzneimitteln: Ein Problem bei der Therapie. Internist (Berlin) 19:366–374

    CAS  Google Scholar 

  • Killick-Kendrick R, Peters W (1978) Rodent malaria. Academic, London, p 406

    Google Scholar 

  • Krotoski WA, Garnham PCC, Bray RS, Krotoski DM, Killick-Kendrick R, Draper CC, Targett GAT, Guy WM (1980) The hypnozoite of Plasmodium cynomolgi: true latent stage in malarial relapse? 29 th Annual meeting. Am Soc Trop Med Hyg, Atlanta

    Google Scholar 

  • Lasagna L (1975) Clinical trials of drugs from the viewpoint of the academic investigator (a satire). Clin Pharmacol Ther 18:629–633

    PubMed  CAS  Google Scholar 

  • Lasagna L (1979) The diseases and drug needs of the Third World. J Chronic Dis 32:413–414

    Article  PubMed  CAS  Google Scholar 

  • Liss RL, Kensler CJ (1976) Advances in modern toxicology. In: Mehlman MA, Shapiro RE, Blumenthal H (eds) New concepts in safety evaluation. Hemisphere, Washington, DC, p273

    Google Scholar 

  • Lupascu G (1974) Applications actuelles de la malaria thérapie. Bull WHO 50:165–168

    PubMed  CAS  Google Scholar 

  • Mannweiler E, Mohr W, Felde I zum, Hinrichs A, Haas J (1976) Zur Serodiagnostik der Malaria. MMW 118:1139–1144

    CAS  Google Scholar 

  • Merkli B, Richie R (1980) Studies on the resistance to single and combined antimalarials in the Plasmodium berghei mouse model. Acta Trop (Basel) 37:228–231

    CAS  Google Scholar 

  • Merkli B, Richie R, Peters W (1980) The inhibitory effect of a drug combination on the development of mefloquine resistance in Plasmodium berghei. Ann Trop Med Parasitol 74:1–9

    PubMed  CAS  Google Scholar 

  • Meuwissen JHET, Leeuwenberg ADEM, Voller A, Matola Y (1974) Specificity of the indirect haemagglutination test with Plasmodium falciparum test cells. Bull WHO 50:513–519

    PubMed  CAS  Google Scholar 

  • Miller LH, Glew RH, Wyler DJ, Howard WA, Collins WE, Contacos PG, Neva FA (1974) Evaluation of clindamycin in combination with quinine against multidrug-resistant strains of Plasmodium falciparum. Am J Trop Med Hyg 23:565–569

    PubMed  CAS  Google Scholar 

  • Mu JY, Iraili ZH, Dayton PG (1975) Studies of the disposition and metabolism of mefloquine HCl (WR 142490), a quinoline-methanol antimalarial, in the rat. Drug Metab Dispos 3:198–210

    PubMed  CAS  Google Scholar 

  • Peters W (1970) Chemotherapy and drug resistance in malaria. Academic, New York

    Google Scholar 

  • Peters W (1979) 4- and 8-Aminoquinoline, Chinin und Chinin-ähnliche Verbindungen. Hahnenklee Symposium Roche Grenzach, BRD

    Google Scholar 

  • Picq JJ, Charmot G, Ricosse JH (1972) A comparative study between a single dose of py-rimethamine-sulfamethopyrazine compound and a single dose of chloroquine for the treatment of acute attack of P. falciparum malaria in “semi-immune” subjects living in an endemic area (Bobo-Dioulasso, Upper Volta). Méd Trop 32:527–546

    CAS  Google Scholar 

  • Powell RD, Brewer GJ (1967) Effects of pyrimethamine, chlorguanide, and primaquine against exoerythrocytic forms of a strain of chloroquine-resistant Plasmodium falciparum from Thailand. Am J Trop Med Hyg 16:693–698

    PubMed  CAS  Google Scholar 

  • Rawlins MD (1974) Variability of response to drugs in man. Br J Hosp Med 803–811

    Google Scholar 

  • Rieckmann KH (1971) Determination of the drug sensitivity of Plasmodium falciparum. JAMA 217:573–578

    Article  PubMed  CAS  Google Scholar 

  • Rieckmann KH, McNamara JV, Frischer H, Stockert TA, Carson PE, Powell RD (1968) Effects of chloroquine, quinine, and cycloguanil upon the maturation of asexual erythrocytic forms of two strains of Plasmodium falciparum in vitro. Am J Trop Med Hyg 17:661–671

    PubMed  CAS  Google Scholar 

  • Rieckmann KH, Trenholme GM, Williams RL, Carson PE, Frischer H, Desjardins RE (1974) Prophylactic activity of mefloquine hydrochloride (WR 142490) in drug-resistant malaria. Bull WHO 51:375–377

    PubMed  CAS  Google Scholar 

  • Rieder J (1976) The simultaneous quantitative determination of total, “active,” acetylated and conjugated sulfonamide in biological fluids. Chemotherapy 22:84–87

    Article  PubMed  CAS  Google Scholar 

  • Rozman RS, Molek NA, Koby R (1978) The absorption, distribution, and excretion in mice of the antimalarial mefloquine, erythro-2,8-bis(trifluoromethyl)-α-(2-piperidyl)-4-quinoline-methanol hydrochloride. Drug Metab Dispos 6:654–658

    PubMed  CAS  Google Scholar 

  • Schwartz DE (1980) Quantitative determination of the antimalarial drug mefloquine and of its main metabolite in plasma by direct densitometric measurement on TLC plates. In: Frigerio, McCamish (eds) Recent developments in chromatography and electrophoresis, vol 10. Elsevier, Amsterdam, pp 69–74

    Google Scholar 

  • Schwartz DE, Weber W, Richard-Lenoble D, Gentillini M (1980) Kinetic studies of mefloquine and one of its metabolites, Ro 21–5104, in the dog and in man. Acta Trop (Basel) 37:238–242

    CAS  Google Scholar 

  • Schwartz DE, Eckert G, Hartmann D, Weber B, Richard-Lenoble D, Ekue JMK, Gentilini M (1982) Single-dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites. Chemotherapy 28:70–84

    Article  PubMed  CAS  Google Scholar 

  • Smith CC, Weigel WW, Wolfe GF (1973) Excretion and tissue localization patterns of experimental antimalarial agents. Fed Proc 32:701

    Google Scholar 

  • Staiger MA, Nguyen-Dinh P, Churchill C (1981) Sensitive high-performance liquid chromatographic analysis for chloroquine in body fluids. Application to studies of drug resistance in Plasmodium falciparum. J Chromatogr 225:139–149

    Article  PubMed  CAS  Google Scholar 

  • Trenholme GM, Williams RL, Desjardins RE, Frischer H, Carson PE, Rieckmann KH, Canfield CJ (1975) Mefloquine (WR 142490) in the treatment of human malaria. Science 190:792–794

    Article  PubMed  CAS  Google Scholar 

  • Ungureanu E, Killick-Kendrick R, Garnham PCC, Branzei P, Romanescu C, Shute PG (1976) Prepatent periods of a tropical strain of Plasmodium vivax after inoculations of tenfold dilutions of sporozoites. Trans R Soc Trop Med Hyg 70:482–483

    Article  PubMed  CAS  Google Scholar 

  • Wernsdorfer WH (1980) Field evaluation of drug resistance in malaria. In vitro micro-test. Acta Trop (Basel) 37:222–227

    CAS  Google Scholar 

  • WHO (1961) Chemotherapy of malaria. WHO Tech Rep Ser 226

    Google Scholar 

  • WHO (1968) WHO expert committee on malaria. 14 th Report. Tech Rep Ser 382

    Google Scholar 

  • WHO (1973) Chemotherapy of malaria and resistance to antimalarials. WHO Tech Rep Ser 529

    Google Scholar 

  • WHO (1974) Symposium on Malaria Research. Bull WHO 50:1–372

    Google Scholar 

  • WHO (1975 a) Developments in malaria immunology. WHO Tech Rep Ser 579

    Google Scholar 

  • WHO (1975 b) Guidelines for evaluation of drugs for use in man. WHO Tech Rep Ser 563

    Google Scholar 

  • WHO (1977) USAID/WHO Workshops on the biology and in vitro cultivation of malaria parasites. Bull WHO 55, n. 2–3:121–429

    Google Scholar 

  • WHO (1979) Instruction for the use of the WHO Test Kit for the assessment of the response of Plasmodium falciparum to chloroquine. WHO Document MAP/79.1

    Google Scholar 

  • WHO (1980) The clinical management of acute malaria. WHO Reg Publ SE Asia Ser 9

    Google Scholar 

  • Wilson M, Fife EH Jr, Methews HM, Sulzer AJ (1975) Comparison of the complement fixation, indirect immunofluorescence, and indirect hemagglutination tests for malaria. Am J Trop Med Hyg 24:755–759

    PubMed  CAS  Google Scholar 

  • Wiselogle FY (1946) A survey of antimalarial drugs 1941–1945. Edwards, Ann Arbor

    Google Scholar 

Download references

Authors
  1. M. Fernex
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, Great Britain

    Wallace Peters M.D., DSc, FRCP, DTM & H (Professor of Medical Protozoology) (Professor of Medical Protozoology)

  2. Scientific Advisory Services, Wellcome Research Laboratories, Ravens Lane, Berkhamsted, Herts., HP4 2DY, Great Britain

    William H. G. Richards BSc, Ph.D. (Manager) (Manager)

Rights and permissions

Reprints and permissions

Copyright information

© 1984 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Fernex, M. (1984). Clinical Trials — Phases I and II. In: Peters, W., Richards, W.H.G. (eds) Antimalarial Drugs I. Handbook of Experimental Pharmacology, vol 68 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69251-2_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69251-2_13

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-69253-6

  • Online ISBN: 978-3-642-69251-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation