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Pharmacokinetics of the diastereomers of arteether, a potent antimalarial drug, in rats
Author(s) -
Sabarinath S.,
Madhusudanan K. P.,
Gupta R. C.
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.452
Subject(s) - pharmacokinetics , dihydroartemisinin , oral administration , pharmacology , in vivo , intramuscular injection , metabolite , chemistry , route of administration , bioavailability , medicine , stereochemistry , artemisinin , biology , immunology , biochemistry , microbiology and biotechnology , malaria , plasmodium falciparum
The pharmacokinetics of α ‐ and β ‐ diastereomers of arteether, a potent erythrocytic schizontocidal agent, and their active metabolite dihydroartemisinin were studied in male Sprague‐Dawley rats after oral, intramuscular and intravenous administrations. Oral and intramuscular studies were carried out at three dose levels at 9, 17.5 and 30 mg kg −1 . The ratio of α ‐ and β ‐isomers was maintained at 30:70% w/w in the formulations used for the study. The average oral bioavailabilities of α ‐and β ‐isomers, relative to intramuscular administration, were 9.6% and 3.8%, respectively, and the average in vivo α ‐ to β ‐ ratio was 2.5. Following intravenous and intramuscular administrations the in vivo α ‐ to β ‐ ratios were 0.7 and 0.9, respectively. The β ‐isomer of arteether was characterized by a longer elimination half‐life and a relatively larger volume of distribution than the α ‐isomer, suggesting that β ‐arteether may be responsible for the prolonged in vivo schizontocidal activity. The α ‐isomer was absorbed rapidly after oral and intramuscular administrations and showed higher peak plasma concentrations but possessed a relatively shorter half‐life. There was an apparent lack of linearity observed in terms of dose and AUCs for both α ‐ and β ‐arteether after oral and intramuscular administrations, suggesting nonlinear dose dependent pharmacokinetics at the dose levels studied. The rate and extent of conversion of arteether isomers to dihydroartemisinin was highest with oral and intravenous administration and least with intramuscular indicating that the intramuscular route of administration of the isomeric mixture may be more beneficial for malarial chemotherapy. Copyright © 2005 John Wiley & Sons, Ltd.