Administration, Rectal

Publication Title: 
British Journal of Clinical Pharmacology

1. The pharmacokinetic and effect kinetic properties of oral (p.o.), intramuscular (i.m.), and intrarectal (i.r.) artemether (5 mg kg-1) were compared in a crossover study in eight healthy adult volunteers. Plasma concentrations of artemether (AM) and its active metabolite dihydroartemisinin (DHA) were measured by high performance liquid chromatography with reductive mode electrochemical detection (h.p.l.c.-ECD), and plasma antimalarial activity in vitro (effect) was assessed on the same samples by a sensitive bioassay (BA). 2.

Author(s): 
Teja-Isavadharm, P.
Nosten, F.
Kyle, D. E.
Luxemburger, C.
ter Kuile, F.
Peggins, J. O.
Brewer, T. G.
White, N. J.
Publication Title: 
Antimicrobial Agents and Chemotherapy

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).

Author(s): 
Krishna, S.
Planche, T.
Agbenyega, T.
Woodrow, C.
Agranoff, D.
Bedu-Addo, G.
Owusu-Ofori, A. K.
Appiah, J. A.
Ramanathan, S.
Mansor, S. M.
Navaratnam, V.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

One hundred and fifty patients with severe falciparum malaria were administered sequential combination of dihydroartemisinin suppository followed by an oral mefloquine tablet. Dihydroartemisinin suppositories (80 mg/capsule) were given rectally once daily for 3 days with a total dose of 8-10 mg/kg. Two doses of mefloquine, 15 mg/kg/dose and 10 mg/kg/dose, were given at 72 hr and 84 hr, respectively. The mean [SD] parasite clearance time and fever clearance time were 46.1 [15.7] hr and 82.5 [59.6] hr, respectively. No death or major adverse drug effects occurred.

Author(s): 
Wilairatna, P.
Krudsood, S.
Silachamroon, U.
Singhasivanon, P.
Vannaphan, S.
Faithong, S.
Klabprasit, M.
Bangchang, S. N.
Olliaro, P.
Looareesuwan, S.
Publication Title: 
British Journal of Clinical Pharmacology

AIMS: To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration. METHODS: Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the alternative preparation given 8 h later in an open crossover design. A further 12 patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later. RESULTS: Following i.v.

Author(s): 
Ilett, Kenneth F.
Batty, Kevin T.
Powell, Shane M.
Binh, Tran Quang
Thu, Le Thi Anh
Phuöng, Hoang Lan
Hung, Nguyen Canh
Davis, Timothy M. E.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Documentation on the efficacy of artesunate in Africa is limited, and no experience of artesunate use in Sudan is documented. Severe malaria in rural areas of Sudan, where facilities for the safe and effective use of parenteral quinine are lacking, is a frequent problem. Early treatment with artesunate suppositories would provide a simple method for use by unskilled staff and would be an alternative approach to treat malaria in settings with poor resources.

Author(s): 
Awad, M. I.
Alkadru, A. M. Y.
Behrens, R. H.
Baraka, O. Z.
Eltayeb, I. B.
Publication Title: 
BMJ (Clinical research ed.)

OBJECTIVE: To compare the efficacy and safety of rectal artemether with intravenous quinine in the treatment of cerebral malaria in children. DESIGN: Randomised, single blind, clinical trial. SETTING: Acute care unit at Mulago Hospital, Uganda's national referral and teaching hospital in Kampala. PARTICIPANTS: 103 children aged 6 months to 5 years with cerebral malaria. INTERVENTION: Patients were randomised to either intravenous quinine or rectal artemether for seven days.

Author(s): 
Aceng, Jane Ruth
Byarugaba, Justus S.
Tumwine, James K.
Publication Title: 
BMC public health

BACKGROUND: Malaria is a serious illness among children aged 5 years and below in Zambia, which carries with it many adverse effects including anemia and high parasites exposure that lead to infant and childhood mortality. Due to poor accessibility to modern health facilities, malaria is normally managed at home using indigenous and cosmopolitan medicines.

Author(s): 
Kaona, Frederick A. D.
Tuba, Mary
Publication Title: 
PLoS medicine

BACKGROUND: Intra-rectal artesunate has been developed as a potentially life-saving treatment of severe malaria in rural village settings where administration of parenteral antimalarial drugs is not possible. We studied the population pharmacokinetics of intra-rectal artesunate and the relationship with parasitological responses in patients with moderately severe falciparum malaria.

Author(s): 
Simpson, Julie A.
Agbenyega, Tsiri
Barnes, Karen I.
Di Perri, Gianni
Folb, Peter
Gomes, Melba
Krishna, Sanjeev
Krudsood, Srivicha
Looareesuwan, Sornchai
Mansor, Sharif
McIlleron, Helen
Miller, Raymond
Molyneux, Malcolm
Mwenechanya, James
Navaratnam, Visweswaran
Nosten, François
Olliaro, Piero
Pang, Lorrin
Ribeiro, Isabela
Tembo, Madalitso
van Vugt, Michèle
Ward, Steve
Weerasuriya, Kris
Win, Kyaw
White, Nicholas J.
Publication Title: 
PloS One

OBJECTIVES: Preparatory to a community trial investigating how best to deliver rectal artesunate as pre-referral treatment for severe malaria; local understanding, perceptions of signs/symptoms of severe malaria and treatment-seeking patterns for and barriers to seeking biomedical treatment were investigated. METHODOLOGY/PRINCIPAL FINDINGS: 19 key informant interviews, 12 in-depth interviews and 14 focus group discussions targeting care-givers, opinion leaders, and formal and informal health care providers were conducted.

Author(s): 
Warsame, Marian
Kimbute, Omari
Machinda, Zena
Ruddy, Patricia
Melkisedick, Majaha
Peto, Thomas
Ribeiro, Isabela
Kitua, Andrew
Tomson, Göran
Gomes, Melba
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

Community-based interventions using artemisinin-derived suppositories may potentially reduce malaria-related childhood mortality. However, their sociocultural acceptability is unknown in Papua New Guinea and a formal examination of caregiver's attitudes to rectal administration was needed to inform effective deployment strategies. Caregivers (n = 131) of children with uncomplicated malaria were questioned on their prior experience with, and attitudes to, rectal administration and then offered artesunate suppositories as treatment of their child.

Author(s): 
Hinton, Rachael L.
Auwun, Alma
Pongua, Grace
Oa, Olive
Davis, Timothy M. E.
Karunajeewa, Harin A.
Reeder, John C.

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