Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in Healthy Adults

Salman, Sam, Bendel, Daryl, Lee, Toong C., Templeton, David and Davis, Timothy M. E. (2015) Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in Healthy Adults. Antimicrobial Agents and Chemotherapy, 59 6: 3197-3207. doi:10.1128/AAC.05013-14

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Author Salman, Sam
Bendel, Daryl
Lee, Toong C.
Templeton, David
Davis, Timothy M. E.
Title Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in Healthy Adults
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2015-03-23
Year available 2015
Sub-type Article (original research)
DOI 10.1128/AAC.05013-14
Open Access Status File (Publisher version)
Volume 59
Issue 6
Start page 3197
End page 3207
Total pages 11
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Collection year 2016
Language eng
Formatted abstract
The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in two open-label studies. In study 1, 16 healthy males were randomized to each of four single-dose treatments administered in random order: (i) 15.0 mg of sublingual artemether (5 × 3.0 actuations), (ii) 30.0 mg of sublingual artemether (10 × 3.0 mg), (iii) 30.0 mg of sublingual artemether (5 × 6.0 mg), and (iv) 30.0 mg of artemether in tablet form. In study 2, 16 healthy males were randomized to eight 30.0-mg doses of sublingual artemether given over 5 days as either 10 3.0-mg or 5 6.0-mg actuations. Frequent blood samples were drawn postdose. Plasma artemether and dihydroartemisinin levels were measured using liquid chromatography-mass spectrometry. Population compartmental pharmacokinetic models were developed. In study 1, sublingual artemether absorption was biphasic, with both rate constants being greater than that of the artemether tablets (1.46 and 1.66 versus 0.43/h, respectively). Relative to the tablets, sublingual artemether had greater bioavailability (≥1.24), with the greatest relative bioavailability occurring in the 30.0-mg dose groups (≥1.58). In study 2, there was evidence that the first absorption phase accounted for between 32% and 69% of the total dose and avoided first-pass (FP) metabolism, with an increase in FP metabolism occurring in later versus earlier doses but with no difference in bioavailability between the dose actuations. Sublingual artemether is more rapidly and completely absorbed than are equivalent doses of artemether tablets in healthy adults. Its disposition appears to be complex, with two absorption phases, the first representing pregastrointestinal absorption, as well as dose-dependent bioavailability and autoinduction of metabolism with multiple dosing.
Keyword Uncomplicated Falciparum malaria
Population Pharmacokinetics
Clinical Pharmacokinetics
Intramuscular
Artemether
Artemisinin derivatives
Dose pharmacokinetics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Centre for Integrated Preclinical Drug Development Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 10 Sep 2015, 13:15:48 EST by Lissi George on behalf of Centre for Integrated Preclinical Drug Development