Pharmacokinetics and bioavailability of oral and intramuscular artemether

Abstract

Both oral and intramuscular artemether were well-tolerated. In most cases, artemether and dihydroartemisinin were detected in plasma after 30 min and declined to levels below the limit of detection within 18-24 h. Compared with intramuscular administration, oral administration of artemether resulted in a relatively rapid but incomplete absorption [Cmax: 474 vs 540 ng.ml-1; tmax: 2.0 vs 3.9 h; AUC: 2.17 vs 5.20 micrograms.h.ml-1]. Geographic means of lag-time and absorption half-life (t1/2a) of oral vs intramuscular artemether were 0.28 and 1.1 h vs 0.30 and 2 h, respectively, t1/2z was significantly shortened after the oral dose [2.8 vs 6.9 h]. Mean oral bioavailability relative to intramuscular administration was 43.2%. The ratio of the AUCs of artemether to dihydroartemisinin was significantly lower after the oral than after the intramuscular dose (geometric mean: 0.29 vs 0.60). artemisinin, which is commercially available in China, Vietnam, Thailand and some African countries. The drug is administered as solution in oil for intramuscular injection or as oral tablets. The clinical efficacy of artemether is dependent on the formulation, dosing scheme, duration of treatment, and the severity of the disease [1, 2]. Oral artemether is effective but with short-term treatment, the relapse rate is high. While the efficacy of intramuscular artemether against multidrug-resistant P. falciparum in either uncomplicated or severe cases has been confirmed, its pharmacokinetic documentation is limited. Formulations with high bioavailability and low costs are essential. With high-performance liquid chromatography and electrochemical detection, more sensitive and reliable assay of artemisinin and derivatives in biological fluids has been achieved [3-4]. In the present study, we have assessed the pharmacokinetics and bioavailability of oral and intramuscular artemether, in healthy Thai males.

Comparative Pharmacokinetics of Intramuscular Artesunate and Artemether in Patients with Severe Falciparum Malaria

“…A third study involving 17 Thai adults with severe malaria, carried out by the same group as the first volunteer study described above (9), reported that the dose-adjusted AUC of ARM was increased in cases of severe malaria, especially in patients with renal impairment (10). All subjects had plasma concentration profiles of both ARM and DHA that exhibited the same pattern as observed in healthy subjects (9), with t max values all close to 4 h, and concentrations in plasma that fell progressively thereafter to levels that were below, or close to, the limit of detection at 24 h (10).…”

Artemether Bioavailability after Oral or IntramuscularAdministration in Uncomplicated FalciparumMalaria

“…Precise oral dosing was provided by taking the powder from 40-mg artemether capsules (Kunming Pharmaceutical Factory), weighing it, and replacing the weight-adjusted amount back in the capsule. Blood samples were taken through an indwelling forearm vein catheter at 0, 15, 30, 45, 60, 90, and 120 min and then 3,4,6,8,12,18, and 24 h following drug administration. A second dose of artemether (2 mg/kg) was then given at 24 h by the alternative route.…”

Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application

“…It interacts with drugs that increase the QT interval and has numerous adverse effects such as nausea, vomiting, skin eruption, elevated SGPT and SGOT due to large doses (100 mg b. d). Pharmacokinetics of ART suggests that its clinical efficacy is dependent on the formulation [16,17]. However, in addition to urgent need for new and effective anti-malarial agents, there is also crucial need to utilize the existing drugs through the concept of novel drug delivery systems with the intention of reducing the dose-induced side effects, while achieving enhanced aqueous solubility, active targeting of diseased tissues, increased bioavailability and above all, patient-friendly dosage regimens to enhance compliance and reduce resistance due to non-compliance.…”

“…In view of this, nanostructured lipid carrier (NLC) appear to be an attractive approach for the delivery of highly lipophilic drugs such as ART as NLCs have advantages over all other colloidal systems -SLNs, SLMs, liposomes, nanoemulsions, microemulsions [15][16][17][18][19][20]. This is because the majority of drugs have higher solubility in liquid lipids (oils) rather than solid lipids.…”