Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, February 2001, p. 509-516, Vol. 45, No. 2
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.2.509-516.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Bioavailability and Preliminary Clinical Efficacy
of Intrarectal Artesunate in Ghanaian Children with Moderate
Malaria
Sanjeev
Krishna,1,*
Tim
Planche,1
Tsiri
Agbenyega,2,3
Charles
Woodrow,1
Dan
Agranoff,1
George
Bedu-Addo,3
Alex K.
Owusu-Ofori,3
John Adabie
Appiah,3
Surash
Ramanathan,4
Sharif M.
Mansor,4 and
Visweswaran
Navaratnam4
Department of Infectious Diseases, St.
George's Hospital Medical School, London SW17 ORE, United
Kingdom1; Department of Physiology,
University of Science and Technology, School of Medical
Sciences,2 and Departments of Child
Health and Medicine, Komfo-Anokye Teaching
Hospital,3 Kumasi, Ghana; and
University Sains Malaysia, 1800 USM, Pulau Pinang,
Malaysia4
Received 14 July 2000/Returned for modification 17 October
2000/Accepted 12 November 2000
We report the first detailed pharmacokinetic assessment of
intrarectal (i.r.) artesunate (ARS) in African children. Artesunate was
given intravenously (i.v.; 2.4 mg/kg of body weight) and i.r. (10 or 20 mg/kg formulated as 50- or 200-mg suppositories [Rectocaps]) in a
crossover study design to 34 Ghanaian children with moderate falciparum
malaria. The median relative bioavailability of dihydroartemisinin (DHA), the active antimalarial metabolite of ARS, was higher in the
low-dose i.r. group (10 mg/kg) than in the high-dose i.r. group (20 mg/kg) (58 versus 23%; P = 0.018). There was wide
interpatient variation in the area under the concentration-time curve
after i.r. ARS administration (up to 9-fold in the high-dose group and 20-fold in the low-dose group). i.r. administered ARS was more rapidly
absorbed in the low-dose group than the high-dose group (median
[range] absorption half-lives, 0.7 h [0.3 to 1.24 h] versus 1.1 h [0.6 to 2.7 h] [P = 0.023]. i.r.
administered ARS was eliminated with a median (range) half-life of
0.8 h (0.4 to 2.7 h) (low-dose group and 0.9 h (0.1 to
2.5 h) (high-dose group) (P = 1). The fractional
clearances of DHA were 3.9, 2.6, and 1.5 liters/kg/h for the 20-mg/kg,
10-mg/kg and i.v. groups, respectively (P = 0.001 and
P = 0.06 for the high-and low-dose i.r. groups compared with the i.v. groups, respectively). The median volumes of distribution for DHA were 1.5 liters kg (20 mg/kg, i.r. group), 1.8 liters/kg (10 mg/kg, i.r. group), and 0.6 liters/kg (i.v. group) (P < 0.05 for both i.r. groups compared with the i.v. group). Parasite
clearance kinetics were comparable in all treatment groups. i.r.
administered ARS may be a useful alternative to parenterally
administered ARS in the management of moderate childhood malaria and
should be studied further.
*
Corresponding author. Mailing address: Department of
Infectious Diseases, St. George's Hospital Medical School, Cranmer
Terr., London SW17 ORE, United Kingdom. Phone: (020) 8725 5827. Fax: (020) 8725 3487. E-mail: s.krishna{at}sghms.ac.uk.
Antimicrobial Agents and Chemotherapy, February 2001, p. 509-516, Vol. 45, No. 2
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.2.509-516.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Kitua, A., Folb, P., Warsame, M., Binka, F., Faiz, A., Ribeiro, I., Peto, T., Gyapong, J., Yunus, E. B., Rahman, R., Baiden, F., Clerk, C., Mrango, Z., Makasi, C., Kimbute, O., Hossain, A., Samad, R., Gomes, M.
(2010). The use of placebo in a trial of rectal artesunate as initial treatment for severe malaria patients en route to referral clinics: ethical issues. J. Med. Ethics
36: 116-120
[Abstract]
[Full Text]
-
Sinou, V., Taudon, N., Mosnier, J., Aglioni, C., Bressolle, F. M. M., Parzy, D.
(2008). Pharmacokinetics of artesunate in the domestic pig. J Antimicrob Chemother
62: 566-574
[Abstract]
[Full Text]
-
Karunajeewa, H. A., Manning, L., Mueller, I., Ilett, K. F., Davis, T. M. E.
(2007). Rectal Administration of Artemisinin Derivatives for the Treatment of Malaria. JAMA
297: 2381-2390
[Abstract]
[Full Text]
-
HINTON, R. L., AUWUN, A., PONGUA, G., OA, O., DAVIS, T. M. E., KARUNAJEEWA, H. A., REEDER, J. C.
(2007). CAREGIVERS' ACCEPTANCE OF USING ARTESUNATE SUPPOSITORIES FOR TREATING CHILDHOOD MALARIA IN PAPUA NEW GUINEA. Am J Trop Med Hyg
76: 634-640
[Abstract]
[Full Text]
-
POLAGE, C. R., BEDU-ADDO, G., OWUSU-OFORI, A., FRIMPONG, E., LLOYD, W., ZURCHER, E., HALE, D., PETTI, C. A.
(2006). LABORATORY USE IN GHANA: PHYSICIAN PERCEPTION AND PRACTICE.. Am J Trop Med Hyg
75: 526-531
[Abstract]
[Full Text]
-
Karunajeewa, H. A., Reeder, J., Lorry, K., Dabod, E., Hamzah, J., Page-Sharp, M., Chiswell, G. M., Ilett, K. F., Davis, T. M. E.
(2006). Artesunate Suppositories versus Intramuscular Artemether for Treatment of Severe Malaria in Children in Papua New Guinea. Antimicrob. Agents Chemother.
50: 968-974
[Abstract]
[Full Text]
-
Whitty, C. J M, Ansah, E., Reyburn, H.
(2005). Treating severe malaria. BMJ
330: 317-318
[Full Text]
-
Woodrow, C J, Haynes, R K, Krishna, S
(2005). Artemisinins. Postgrad. Med. J.
81: 71-78
[Abstract]
[Full Text]
-
Pussard, E., Straczek, C., Kabore, I., Bicaba, A., Balima-Koussoube, T., Bouree, P., Barennes, H.
(2004). Dose-Dependent Resorption of Quinine after Intrarectal Administration to Children with Moderate Plasmodium falciparum Malaria. Antimicrob. Agents Chemother.
48: 4422-4426
[Abstract]
[Full Text]
-
Karunajeewa, H. A., Ilett, K. F., Dufall, K., Kemiki, A., Bockarie, M., Alpers, M. P., Barrett, P. H., Vicini, P., Davis, T. M. E.
(2004). Disposition of Artesunate and Dihydroartemisinin after Administration of Artesunate Suppositories in Children from Papua New Guinea with Uncomplicated Malaria. Antimicrob. Agents Chemother.
48: 2966-2972
[Abstract]
[Full Text]
-
Winstanley, P., Ward, S., Snow, R., Breckenridge, A.
(2004). Therapy of Falciparum Malaria in Sub-Saharan Africa: from Molecule to Policy. Clin. Microbiol. Rev.
17: 612-637
[Abstract]
[Full Text]
-
Nealon, C., Dzeing, A., Muller-Romer, U., Planche, T., Sinou, V., Kombila, M., Kremsner, P. G., Parzy, D., Krishna, S.
(2002). Intramuscular Bioavailability and Clinical Efficacy of Artesunate in Gabonese Children with Severe Malaria. Antimicrob. Agents Chemother.
46: 3933-3939
[Abstract]
[Full Text]