Abstract
The pharmacokinetics of quinine were studied in six Nigerian patients during acute uncomplicated falciparum malaria and convalescent periods. An oral dose of 10 mg/kg quinine dihydrochloride administered 8‐hourly for 7 days gave parasite and fever clearance times of 36.0 ± 16.6 h and 18.0 ± 6.4 h, respectively. From the individual quinine plasma profiles the mean plasma concentration of quinine at the time of parasite clearance was estimated as 4.5 ± 1.1 μg/ml. Plasma quinine levels during malaria rose rapidly reaching a peak around the second and third days and declining thereafter as patients improved clinically. In acute malaria plasma quinine levels were more than two-fold higher than in convalescence; the mean AUC(0-12) in malaria was 37.9 ± 14.7 μg.h/ml compared to 17.9 ± 8.5μg.h/ml in convalescence. The apparent oral clearance (CL/F) and volume of distribution (Vd/F) duri ng the acute phase of the malaria (1.9 ± 0.7 ml/min/kg and 1.8 ± 0.9 l/kg, respectively) were significantly lower than in convalescence (4.5 ± 2.1 ml/min/kg and 4.2 ± 3.2 l/kg). The present data suggest that malaria parasites in African patients are still very sensitive to quinine and that the current dosage of quinine is effective for the treatment of acute falciparum malaria in African patients without augmenting therapy with any other drug such as tetracycline or sulphadoxine-pyrimethamine. It also confirms that malaria significantly alters the pharmacokinetics of quinine in humans.
Similar content being viewed by others
References
World Health Organisation. Weekly Epidemiological Record 1989;16:399–403.
Ekanem OJ. Plasmodium falciparum not responding to chloroquine in Nigeria. Trans Roy Soc Trop Med Hyg 1985;79:141.
Salako LA, Aderounmu AF. In vitro chloroquine and mefloquine resistant Plasmodium falciparum in Nigeria. Lancet 1987; ii:572–3.
World Health Organisation. Practical chemotherapy of malaria. Technical Report Series 1990, Geneva; 805p.
White NJ, Looareesuwan S, Warrel DA, Warrel MJ, Bunnag D, Harinasuta T. Quinine pharmacokinetics and toxicity in cerebral and uncomplicated falciparum malaria. Am J Med 1982;73:564–72.
Supanaranond W, Davis TME, Prukrittayakemee S, Silamut K. Disposition of oral quinine in acute falciparum malaria. Eur J Clin Pharmac 1991;40:49–52.
Salako LA. Quinine and Malaria: the African experience. Acta Leidensia 1987;55:167–80.
Salako LA, Sowunmi A, Laoye O. Evaluation of the sensitivity in vivo and in vitro of Plasmodium falciparum in malaria to quinine in an area of full sensitivity to chloroquine. Trans Roy Soc Trop Med Hyg 1988;82:366–8.
Pasvol G, Newton CR, Winstanley PA, Watkins WM, Peshu NM, Were JB, et al. Quinine treatment of severe falciparum malaria in African children: a randomized comparison of three regimens. Am J Trop Med Hyg 1991;45:702–13.
Mansor SM, Taylor TE, McGrath CS, Edwards G, Ward SA, Wirima JJ, et al. The safety and kinetics of intramuscular quinine in Malawian children with severe falciparum malaria. Trans Roy Soc Trop Med Hyg 1991;84:482–7.
Couet W, Laroche R, Floch J, Istin B, Fourtillan J, Sauniere J. Pharmacokinetics of quinine and doxicycline in patients with acute falciparum malaria: A study in Africa. Ther Drug Monit 1991;13:496–501.
White NJ. The pharmacokinetics of quinine in malaria. Acta Leidensia 1987;55:65–76.
Babalola CP, Bolaji OO, Dixon PAF, Ogunbona FA. Column liquid chromatographic analysis of quinine in human plasma, saliva and urine. J Chromatogr 1993;616:151–4.
Gibaldi M, Perrier D. Pharmacokinetics, 2nd edn. New York: Marcel Dekker, 1982: 409–17.
Metzler KD, Weiner DL. PCNONLIN User's guide, Lexington. Statistical Consultants, 1982 A1–A53.
Jamaludin A, Mohamad M, Mavaratnam V, Selliah K, Tan SC, Wernsdorfer WH, et al. Relative bioavailability of the hydrochloride, sulphate and ethylcarbonate salts of quinine. Br J Clin Pharmacol 1988;25:261–3.
Merkus FW, Smit EH. The use of quinine in the treatment of malaria from the past to future. Int. Pharmacy J 1988;2:47–50.
Peters W. The problem of drug resistance in malaria. Parasitology 1985;90:705–715.
Warhurst DC. Cinchona alkaloids and malaria. Acta Leidensia 1987;55:53–64.
Chongsuphajaisiddhi T, Sabchareon A, Attanath P. Treatment of quinine-resistant falciparum malaria in Thai children. Southeast Asian J Trop Med Publ Hlth 1983;14:357–60.
Silamut K, White NJ, Looareesuwan S, Warrel DA. Binding of quinine to plasma proteins in falciparum malaria. Am J Trop Med Hyg 1985;34:681–6.
Silamut K, Molunto P, Ho M, Davis TM. White NJ. Alpha 1-acid glycoprotein (orosomucoid) and plasma protein binding of quinine in falciparum malaria. Br J Clin Pharmacol 1991;32:311–315.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Babalola, C.P., Bolaji, O.O., Ogunbona, F.A. et al. Pharmacokinetics of quinine in African patients with acute falciparum malaria.. Pharm World Sci 20, 118–122 (1998). https://doi.org/10.1023/A:1008699022244
Issue Date:
DOI: https://doi.org/10.1023/A:1008699022244