Pengubahsuaian kaedah analisis bagi pironaridina di dalam plasma dan perbandingan formulas! pironaridina dalam kajian farmak.okinetik
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Date
1999
Authors
G. Jayaraman, Sarala Devi (a/p)
Journal Title
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Abstract
Pyronaridine is a promising drug for the treatment of uncomplicated malaria and
has been recently received encouraging results in clinical trials conducted in Cameroon
and Thailand. A method is described for the determination of pyronaridine in plasma
using high-performance liquid chromatography with fluorescence detection. The
method involved liquid-liquid extraction using phosphate buffer (pH 6, 0.05M) and
diethyl ether:hexane (70:30 %, v/v) chromatographic separation on a C18 column
(Nucleosil, 250 x 4.6 mm i.d., 5 J.Lm particle size) with acetonitrile and 0.05M phosphate
buffer of pH 6 (60:40%, v/v) as the mobile phase with flow rate at 1.0 mllmin and
detection by fluorescence 0-ex = 267 nm, "-em = 443 nm). The detector's response is
linear up to 1000 ng and the ov~rall recoveries of pyronaridine and quinine were 90.0· .
and 60.3% respectively. The a.Ssay procedure was adequately sensitive to measure 10
ng/ml pyronaridine in plasma samples with acceptable precision ( < 15% CV). The
method was found to be suitable for use in clinical pharmacological studies.
Pyronaridine is currently available as enteric coated (EC) tablets but the
bioavailability is poor (20%). The bioavailability of the drug in capsules appear to be
better (30%). This investigation compares the relative bioavailabilities of pyronaridine
capsule and solution formulations m healthy Thai volunteers. .
A single dose of pyronaridine (6 mg/kg) was given to subjects (n=6) either by capsule or
solution formulations. After a washout period of 19 days, each subject was given
another dose of pyronaridine using the other formulation. Blood plasma samples were
drawn at appropriate time points and samples were stored at -70°C until analysis by
HPLC. Pharmacokinetic parameters were determined from analysis of concentration
time curves of pyronaridine. There were no significant differences in all the parameters
(p>O.OS). In this study pyronaridine solution failed to show a distinct advantage over
the capsule formulation which is easier to use in practice. Relative bioavailability after
administration by capsule formulation relative to the administration by solution
formulation is 111.7%. This value shows that there is little difference in the
bioavailability of the two formulations.
Description
Keywords
Formulas! pironaridina , Farmakokinetik