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. 1987;65(1):51–55.

Increased accumulation of chloroquine and desethylchloroquine in homozygous sickle cells

A U Orjih
PMCID: PMC2490867  PMID: 3495366

Abstract

The effect of haemoglobin genotype on the level of chloroquine in the erythrocytes of homozygous sickle-cell (SS), normal (AA), and heterozygous (AS) subjects was investigated in vivo and in vitro. Two hours after a single oral dose of chloroquine its level in plasma was consistently lower in SS than in AA subjects. In contrast, its level in the erythrocytes was higher in SS than in AA subjects. Desethylchloroquine, a metabolite of chloroquine, was detected only in the erythrocytes of SS blood but was present in both the plasma and erythrocytes of AA blood. For the in vitro test, a 5% suspension of erythrocytes was incubated for 1 hour with a 2.06 μmol/l solution of chloroquine. The mean chloroquine distribution ratio (μmol chloroquine per kg erythrocytes:μmol chloroquine per litre medium) was 31.0, 3.5, and 2.7 for SS, AA, and AS erythrocytes, respectively. The results of the study indicate that haemoglobin genotype appears to influence the level of chloroquine in erythrocytes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adelusi S. A., Dawodu A. H., Salako L. A. Kinetics of the uptake and elimination of chloroquine in children with malaria. Br J Clin Pharmacol. 1982 Oct;14(4):483–487. doi: 10.1111/j.1365-2125.1982.tb02016.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asakura T., Minakata K., Adachi K., Russell M. O., Schwartz E. Denatured hemoglobin in sickle erythrocytes. J Clin Invest. 1977 Apr;59(4):633–640. doi: 10.1172/JCI108681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bergqvist Y., Domeij-Nyberg B. Distribution of chloroquine and its metabolite desethyl-chloroquine in human blood cells and its implication for the quantitative determination of these compounds in serum and plasma. J Chromatogr. 1983 Jan 14;272(1):137–148. doi: 10.1016/s0378-4347(00)86110-1. [DOI] [PubMed] [Google Scholar]
  4. Campwala H. Q., Desforges J. F. Membrane-bound hemichrome in density-separated cohorts of normal (AA) and sickled (SS) cells. J Lab Clin Med. 1982 Jan;99(1):25–28. [PubMed] [Google Scholar]
  5. Chou A. C., Chevli R., Fitch C. D. Ferriprotoporphyrin IX fulfills the criteria for identification as the chloroquine receptor of malaria parasites. Biochemistry. 1980 Apr 15;19(8):1543–1549. doi: 10.1021/bi00549a600. [DOI] [PubMed] [Google Scholar]
  6. Faehlmann M., Rombo L., Hedman P. Serum concentrations of chloroquine in a patient with a late recrudescence of Kenyan Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 1981;75(3):362–364. doi: 10.1016/0035-9203(81)90093-6. [DOI] [PubMed] [Google Scholar]
  7. Fitch C. D. Chloroquine resistance in malaria: a deficiency of chloroquine binding. Proc Natl Acad Sci U S A. 1969 Dec;64(4):1181–1187. doi: 10.1073/pnas.64.4.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Herzog C., Ellis C. J., Innes J. A., Fletcher K. A. Possible role of drug malabsorption in recrudescence of falciparum malaria. Lancet. 1982 Nov 20;2(8308):1157–1158. doi: 10.1016/s0140-6736(82)92807-0. [DOI] [PubMed] [Google Scholar]
  9. Orjih A. U., Chevli R., Fitch C. D. Toxic heme in sickle cells: an explanation for death of malaria parasites. Am J Trop Med Hyg. 1985 Mar;34(2):223–227. doi: 10.4269/ajtmh.1985.34.223. [DOI] [PubMed] [Google Scholar]
  10. Patchen L. C., Mount D. L., Schwartz I. K., Churchill F. C. Analysis of filter-paper-absorbed, finger-stick blood samples for chloroquine and its major metabolite using high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1983 Nov 11;278(1):81–89. doi: 10.1016/s0378-4347(00)84758-1. [DOI] [PubMed] [Google Scholar]
  11. Schwartz I. K., Payne D., Campbell C. C., Khatib O. J. In-vivo and in-vitro assessment of chloroquine-resistant Plasmodium falciparum malaria in Zanzibar. Lancet. 1983 May 7;1(8332):1003–1005. doi: 10.1016/s0140-6736(83)92640-5. [DOI] [PubMed] [Google Scholar]
  12. Verdier F., Clavier F., Deloron P., Blayo M. C. Distribution de la chloroquine et de la déséthyl-chloroquine dans le sang, le plasma et les érythrocytes de sujets sains et paludéens. Dosage en HPLC. Pathol Biol (Paris) 1984 May;32(5):359–361. [PubMed] [Google Scholar]
  13. Walker O., Dawodu A. H., Adeyokunnu A. A., Salako L. A., Alvan G. Plasma chloroquine and desethylchloroquine concentrations in children during and after chloroquine treatment for malaria. Br J Clin Pharmacol. 1983 Dec;16(6):701–705. doi: 10.1111/j.1365-2125.1983.tb02244.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Weniger B. G., Blumberg R. S., Campbell C. C., Jones T. C., Mount D. L., Friedman S. M. High-level chloroquine resistance of Plasmodium falciparum malaria acquired in Kenya. N Engl J Med. 1982 Dec 16;307(25):1560–1562. doi: 10.1056/NEJM198212163072506. [DOI] [PubMed] [Google Scholar]

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