Summary
The pharmacokinetics of artesunate and its major plasma metabolite, dihydroartemisinin, were investigated in 11 Thai male patients with acute uncomplicated falciparum malaria during the acute and recovery phases. Patients were given an oral dose of 200mg artesunate (Guilin Pharmaceutical) on the first day, followed by 100mg 12 hours later, then 100mg daily for another 4 days (total dose of 700mg). All the patients showed a rapid initial response with median (range) parasite and fever clearance times of 30 (18 to 60) and 24 (4 to 94) hours, respectively; no patients showed reappearance of parasites during the 28-day follow-up period. No significant clinical adverse effects were detected in any patient. Acute phase malaria infection significantly influenced the pharmacokinetics of artesunate and its active metabolite, dihydroartemisinin. Maximum plasma drug concentration (Cmax), absorption half-life (t1/2 a), area under the plasma concentration-time curve from zero to the last observed time (AUC) and terminal elimination half-life (t1/2 z) of artesunate were decreased, while apparent total body clearance (CL/f) was increased during the acute phase, compared with the recovery phase. In addition, a decrease in the Cmax and an increase in the AUCdha/ARS ratio were found. Optimisation of therapy with oral artesunate should therefore be based on the kinetics of the drug and dihydroartemisinin in malaria patients with acute phase infection.
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References
Li GQ, Guo XB, Fu LC, et al. Clinical trials of artemisinin and its derivatives in the treatment of malaria in China. Trans R Soc Trop Med Hyg 1994; 88 Suppl.: 5–6
Bunnag D, Viravan C, Looareesuwan S, et al. Double blind randomised clinical trial of two different regimens of oral artesunate in falciparum malaria. Southeast Asian J Trop Med Public Health 1991; 22: 534–8
Bunnag D, Viravan C, Looareesuwan S, et al. Double blind randomised clinical trial of oral artesunate at once or twice daily in falciparum malaria. Southeast Asian J Trop Med Public Health 1991; 22: 539–43
Karbwang J, Na-Bangchang K, Thanavibul A, et al. Comparison of oral artesunate and quinine plus tetracycline in acute uncomplicated falciparum malaria. Bull World Health Organ 1994; 72: 233–8
Karbwang J, Na-Bangchang K, Thanavibul A, et al. Comparative clinical trial of artesunate and the combination artesunate-mefloquine in multidrug resistant falciparum malaria. Clin Drug Invest 1996; 11: 84–9
Hein TT, Arnold K, Vinh H, et al. Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria. Trans R Soc Trop Med Hyg 1992; 86: 582–3
Karbwang J, Mlunto P, Na-Bangchang K, et al. Determination of mefloquine in biological fluids using high performance liquid chromatography. Southeast Asian J Trop Med Public Health 1989; 20: 55–60
Karbwang J, Na-Bangchang K, Molunto P, et al. Determination of quinine and quinidine in biological fluids by high performance liquid chromatography. Southeast Asian J Trop Med Public Health 1989; 20: 65–9
Karbwang J, Na-Bangchang K, Molunto P, et al. Determination of artemether and its major plasma metabolite, dihydro-artemisinin, in plasma using high-performance liquid chromatography with electrochemical detection. J Chromatogr B 1997; 690: 259–65
Na-Bangchang K, Congpuong K, Hung LN, et al. A simple high performance liquid chromatography with electrochemical detection method for simultaneous determination of artesunate and dihydroartemisinin in biological fluids J Chromatogr B Biomed Appl. In press
Gibaldi M, editor. Biopharmaceutics and clinical pharmacokinetics. Philadelphia: Lea and Febiger, 1991: 14–23
Yang S, Ma J, Sun J, et al. Clinical pharmacokinetics of a new effective antimalarial artesunate, a qinghaosu derivative. Chin J Clin Pharmacol 1985; 1: 106–9
Benakis A, Paris M, Plessas C, et al. Pharmacokinetics of sodium artesunate after i.m. and i.V. administration [abstract]. Am J Trop Med Hyg 1993; 293 Suppl.: 23
Benakis A, Paris M, Loutan L, et al. Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers. Am J Trop Med Hyg 1997; 56: 17–23
Batty KT, Davis TME, Thu LTA, et al. Selective high perfomance liquid Chromatographic determination of artesunate and α-β-dihydroartemisinin in patients with malaria. J Chromatogr B 1996; 677: 345–50
Bethell DB, Teja-Isvadharm P, Thanh Phuong CX, et al. Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg 1997; 91: 195–8
Na-Bangchang K, Karbwang J, Congpoung K, et al. Pharmacokinetic and bioequivalence evaluation of the two generic formulations of oral artesunate. Eur J Clin Pharmacol. In press
Karbwang J, Na-Bangchang K, Congpoung K, et al. Pharmacokinetics and bioavailability of oral and intramuscular artemether. Eur J Clin Pharmacol 1997; 52: 307–10
Karbwang J, Na-Bangchang K, Congpoung K, et al. Pharmacokinetics of oral artemether in Thai patients with uncomplicated falciparum malaria. Fund Clin Pharmacokinet. In press
Alin MH, Ashton M, Kihamia CM, et al. Multiple dose pharmacokinetics of oral artemisinin and comparison of its efficacy with that of oral artesunate in falciparum malaria patients. Trans R Soc Trop Med Hyg 1996; 90: 61–5
Lee IS, Hufford CD. Metabolism of antimalarial sesquiterpene lactones. Pharmacol Ther 1990; 48: 345–55
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Karbwang, J., Na-Bangchang, K., Congpoung, K. et al. Pharmacokinetics of Oral Artesunate in Thai Patients with Uncomplicated Falciparum Malaria. Clin. Drug Investig. 15, 37–43 (1998). https://doi.org/10.2165/00044011-199815010-00005
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DOI: https://doi.org/10.2165/00044011-199815010-00005