Link Kim Binh Mai 1996 Dien

Results Following i.v. Bolus, ARTS had a peak concentration of 42 µ m (16 mg l −1), elimination t 1/2 = 3.2 min, CL = 2.8 l h −1 kg −1 and V = 0.22 l kg −1. The C max for DHA was 9.7 µ m (2.7 mg l −1), t 1/2 = 59 min, CL = 0.64 l h −1 kg −1 and V = 0.8 l kg −1. Following i.m. Drum library vol 1. ARTS, C max was 2.3 µ m (3.7 mg l −1), the apparent t 1/2 = 41 min, CL = 2.9 l h −1 kg −1 and V = 2.6 l kg −1. The relative bioavailability of DHA was 88%, C max was 4.1 µ m (1.16 mg l −1) and t 1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was 16%.

Introduction Artemisinin and derivatives such as artesunate and artemether have become an integral component of malaria treatment protocols in many tropical countries, especially where multidrug resistant Plasmodium falciparum has emerged. These artemisinin drugs have different physico-chemical and pharmacokinetic properties and are available in a variety of formulations that influence their routes of administration and dosage regimens [–]. Artesunate (ARTS), the only water-soluble derivative in clinical use, has been administered by the intravenous (i.v.), intramuscular (i.m.), oral and rectal routes at doses ranging from 2 mg kg −1 to more than 6 mg kg −1 [–]. Administration of ARTS is indicated for patients who have severe falciparum malaria, particularly those in coma, venous access may not be possible where only basic health care facilities exist.

Apr 17, 2012 - Mai Bach Le. Le Hung Q, de Vries PJ, Giao PT, Binh TQ, Nam NV, et al. World Health Organization (1996) Indicators for assessing vitamin A deficiency and. Gibson RS (2006) Zinc: the missing link in combating micronutrient. Dien le N, Thang NM, Bentley ME (2004) Food consumption patterns in.

In addition, even when drugs can be given intravenously, patient discomfort and inconvenience, staff time, and risks such as overhydration and thrombophlebitis may make i.v. Less attractive than i.m.

Or rectal administration. The development of i.m. And rectal ARTS regimens is dependent on valid pharmacokinetic data and clinical evidence that use of these routes results in comparable efficacy to i.v. As a first step in this process, we have conducted a pharmacokinetic evaluation of alternative routes of administration of ARTS and its active metabolite dihydroartemisinin (DHA) in patients with uncomplicated falciparum malaria. Pharmacokinetic data for ARTS and DHA, following i.v., oral and rectal administration of ARTS have been published [, –], but there has been no comprehensive pharmacokinetic study of i.m. Hence, our first objective was to determine the pharmacokinetic properties of ARTS and DHA following i.m. ARTS administration to patients with uncomplicated falciparum malaria.

Our second objective was an investigation of the pharmacokinetic properties of DHA suppositories. DHA is the chemical intermediate in the production of ARTS and other semisynthetic artemisinin derivatives [] and their principal active metabolite []. Although DHA is not sufficiently water-soluble to be formulated as an i.v. Injection, it is cheaper to produce than the artemisinin derivatives and is now available as oral tablets and rectal suppositories. We have shown that DHA has a high oral bioavailability in healthy volunteers and comparable bioavailability to oral ARTS in patients with falciparum malaria []. The present study provides the first report of the pharmacokinetic properties of DHA when administered rectally to adult patients with uncomplicated falciparum malaria.

Patients Twenty-four patients with uncomplicated falciparum malaria were recruited from the Bao Loc region of Lam Dong Province in Vietnam. All patients gave written, informed consent in Vietnamese.

The diagnosis was confirmed by microscopic examination of thick and thin blood films, and a complete clinical assessment including drug history was completed. Patients were excluded if they had impaired consciousness, jaundice (serum bilirubin > 50 µmol l −1), renal impairment (serum creatinine > 250 µmol l −1 after rehydration), anaemia (venous haematocrit 150 000 asexual forms per µl whole blood from thick film analysis) or if informed consent could not be obtained. Patients were not recruited if they had been treated with ARTS or DHA in the previous 8 h, artemisinin in the previous 12 h, or artemether in the previous 24 h. These criteria ensured that patients were excluded for a period at least five times the elimination half-life of the drug (approximately 40 min for DHA, 2 h for artemisinin and 4 h for artemether [, ]). The study was approved by the Ministry of Health, Vietnam, and the University of Western Australia Human Rights Committee. Study design and procedures In the intramuscular (i.m.) study, 12 patients were randomized by a predetermined, computer-generated schedule to receive either i.v.

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