Development of Analytical Method for the Determination of a New Antifilarial Drug, CDR 101 in Body Fluids and Its Application in Pharmacokinetic and Clinical Studies.
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Date
1997-04
Authors
Selvamuniandy, Tamil Selvy
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Abstract
CDR 101 is a new anti filarial drug which was selected from screening
under the 01'<TIP/World Bank/WHO Drug Discovery Programme. Information on the
physicochemical and pharmacokinetic properties are unavailable. The objective of this
study is to address these issues. CDR 101 decomposes at 238 - 240 °C with pJ(a
values of5.28 ± 0.31 and 7.49 ± 0.34. It is sensitive towards light. CDR 101 in plasma
is stable at -20 and -70 °C but not at 4 °C. A selective and sensitive highperformance
liquid chromatographic assay for quantitative determination of CDR 101
is described. After extraction from plasma and blood using chloroform, CDR 101 was
analysed using a C18 Nucleosil ODS-2 reverse-phase stainlees steel column and a
mobile phase of acetonitrile-0.05 M ammonium acetate adjusted to pH 3.0 with
ultraviolet detection at 318 nm. The mean recoveries of CDR 101 in plasma and blood
over a concentration range of25- 500 ng/mL were 95.51 ± 2.01% and 83.35 ± 1.87%,
respectively. The within-day and day-to-day coefficients of variations for plasma were
3.23%- 6.21% and 2.59%- 9.90% respectively whereas for blood were 2.89 - 5.92%
and 2.89 - 6.82% respectively. The minimum detectable concentration for CDR 101
in plasma and blood were 1 ng/mL and 2.5 ng/mL respectively. This method was
found to be suitable for clinical pharmacokinetic studies in rats and calves. Following
intravenous administration of a dose of 0.4 mg/kg in rats, CDR 101 was eliminated
from blood with half-life (t 112), clearance(Cl) and volume of distribution (Vd) of
84.7 ± 21.5 min, 69.8 ± 14.4 mL/min/kg and 8.6 ± 3.2 L/kg, respectively. In calves
treated subcutaneously, the pharmacokinetic parameters could not be calculated due to
erratic absorption.. No metabolite peaks were observed in any of the three
pharmacokinetic studies.
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Keywords
Antifilarial Drug