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Pharmacokinetics and Pharmacodynamics of Arterolane Maleate Following Multiple Oral Doses in Adult Patients With P. falciparum Malaria
Author(s) -
Gautam Anirudh,
Ahmed Tausif,
Sharma Pradeep,
Varshney Brijesh,
Kothari Monika,
Saha Nilanjan,
Roy Arjun,
Moehrle Joerg J.,
Paliwal Jyoti
Publication year - 2011
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270010385578
Subject(s) - pharmacokinetics , pharmacodynamics , medicine , pharmacology , malaria , plasmodium falciparum , piperaquine , artemisinin , immunology
Arterolane (RBx 11160) maleate is a novel, rapidly acting synthetic trioxolane antimalarial compound being developed by Ranbaxy Research Laboratories (Haryana, India). It is presently under phase III in combination with piperaquine phosphate. The present work reports the relationship between pharmacokinetic (PK) parameter (AUC 0–8h on day 0/day 6) and indices of pharmacodynamic (PD) response (50% parasite clearance [PC 50 ], 90% parasite clearance [PC 90 ], parasite clearance time [PCT], recrudescence) from a phase II, double‐blind, multicenter, randomized, parallel‐group, dose‐ranging trial. Patients with acute uncomplicated P. falciparum malaria were randomized to 1 of 3 arterolane maleate (50, 100, and 200 mg) doses for 7 consecutive days. Plasma concentration data were available from 78, 76, and 75 patients receiving a 50‐, 100‐, and 200‐mg dose, respectively. Based on PD modeling, its limitations and assumptions, minimum 150‐mg dose arterolane maleate was recommended to optimize the probability of maximum therapeutic benefits for an adult. Doses higher than 100 mg are unlikely to reduce the probability of recrudescence. This study re‐stresses the need of combining short and long‐acting drugs to prevent resistance development and minimize recrudescence.