Malinee Wongnawa

Antinociceptive activity of the methanolic extract of Kaempferia galanga Linn. in experimental animals.

Kaempferia galanga Linn. (Zingiberaceae) presents many chemical constituents of the volatile oil extracted from the rhizome. The rhizome of Kaempferia galanga is used by people in many regions for relieving toothache, abdominal pain, muscular swelling and rheumatism. In this study we investigated the antinociceptive activity in mice and rats using acetic acid-induced writhing, formalin, hot plate and tail-flick tests. The extract at test doses of 50, 100 and 200 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. This activity was dose- and time-dependent. The extract administered at 200 mg/kg, p.o. had a stronger antinociceptive effect than aspirin (100 mg/kg, p.o.) but less than morphine (5 mg/kg, s.c.). Naloxone (2 mg/kg, i.p.) abolished the antinociceptive action of both morphine (5 mg/kg, s.c.) and the extract (200 mg/kg, p.o.) in a similar manner. In conclusion, the methanol extract of Kaempferia galanga markedly demonstrated the antinociceptive action in experimental animals. The antinociceptive mechanisms appear to be both peripherally and centrally mediated actions and the opioid receptors are probably involved. Therefore, our studies support the use in traditional medicine of Kaempferia galanga against pain caused by various disorders.

Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteers

Background:  Antimalarial mefloquine has a structure related to quinine. The major metabolite of quinine is 3‐hydroxyquinine formed by cytochrome P450 3A4 (CYP3A4). Ketoconazole, a potent inhibitor of CYP3A4, is known to markedly increase plasma concentrations of various co‐administered drugs including quinine.

Effect of Rifampin on Plasma Concentrations of Mefloquine in Healthy Volunteers

Mefloquine is a 4‐quinolinemethanol compound structurally related to quinine. Quinine is mainly metabolized by the cytochrome P450 3A4 isozyme (CYP3A4), whereas rifampin, a potent inducer of CYP3A4, is known to markedly decrease plasma quinine concentration. Our aim was to study the effect of rifampin on the pharmacokinetics of mefloquine, and explore a possible role of CYP3A4 on mefloquine metabolism.

Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers

Praziquantel is extensively metabolized by the hepatic cytochrome P450 (CYP) enzymes. The CYP3A isoforms are likely to be major enzymes responsible for praziquantel metabolism. Rifampin (INN, rifampicin), a potent enzyme inducer of CYP‐mediated metabolism (especially CYP2C9, CYP2C19, and CYP3A4), is known to markedly decrease plasma concentrations and effects of a number coadministered drugs. The aim of this investigation was to study the possible pharmacokinetic interaction between rifampin and praziquantel.

Rifampin, a cytochrome P450 3A inducer, decreases plasma concentrations of antipsychotic risperidone in healthy volunteers.

Background:  Although cytochrome P450 (CYP) 2D6 is often thought to be the only CYP responsible for the metabolism of risperidone, many reports suggest that CYP3A may be involved too. Rifampin, a potent CYP3A inducer, has been known to markedly decrease plasma concentrations of various drugs, which are concomitantly administered during treatment.

Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts.

The effects and plausible mechanism of action of Curcuma aeruginosa Roxb. (Zingiberaceae) rhizome chloroform and methanol extracts on the uterine contraction were investigated using isolated uterus strips from estrogen primed rats. The contractile responses were recorded isometrically with a Grass FT03 force transducer connected to a MacLab system. The experiments were carried out on both nonstimulated, agonist- and KCl-stimulated uteri. In the nonstimulated uterus, the two extracts (10-400 microg/ml) had no significant effect. In contrast, in the stimulated uterus, the chloroform and methanol extracts exerted concentration-dependent inhibition of the contractions induced by oxytocin (1 mU/ml), prostaglandin F2alpha (PGF2alpha, 0.5 microg/ml), ACh (3x10(-6) M) and KCl (40 mM) with the IC50 (inhibition of force) of 31.4, 58.59, 56.21 and 29.28 microg/ml; and 57.79, 69.3, 223.8 and 69.19 microg/ml, respectively. Verapamil, the reference L-type calcium channel blocker, exhibited a similar pattern of inhibition with the IC50 of 0.03, 0.25, 0.35 and 0.04 microg/ml. The IC50 of diclofenac against a PGF2alpha-induced contraction was 31.36 microg/ml. It is known that the contraction induced by agonists and KCl is mainly due to calcium influx through the voltage-gated L-type calcium channels opened indirectly or directly by agonist-receptor activation and KCl. Thus, it is speculated that the two plant extracts might inhibit uterine contraction by interrupting the influx of Ca2+ probably through voltage-gated L-type calcium channels. This possibility was further substantiated by the ability of the extracts to shift the CaCl2-contraction curves to the right. As the methanol extract also reduced the contraction of oxytocin in Ca2+-free EDTA solution; thus, it is suggested that part of its action may be involved with an intracellular mechanism. The effect of the two extracts did not involve the activation of beta2-adrenoceptors since their effects were unaffected by propranolol. Based on the inhibitory effect of the extracts on the oxytocin-induced contraction, it is concluded that the extracts might be useful as tocolytic agents for the prevention of preterm labor. Their effects on the inhibition of PGF2alpha-induced contractions also seem useful for the treatment of dysmenorrhea. There are reports by others that the plant rhizome contains beta-pinene and sesquiterpenes. In addition, there is evidence that these compounds possess spasmolytic effects in the rat intestine and uterus. Therefore, the uterine relaxant effect of the plant extracts could be due to beta-pinene and some sesquiterpene lactones contents. The methanol extract is less potent than the chloroform extract, and this might be due to the lower amount of terpene compounds or different compounds may involve in this action.

LC determination of praziquantel in human plasma

A simple high-performance liquid chromatographic (HPLC) method for the determination of praziquantel in human plasma was developed and validated. The present method was described by adding drop-wise 0.2 M Zinc sulfate and acetonitrile to plasma sample for deproteinization. This method used a reversed-phase Spherisorb ODS 2 column (5 microm), 250 x 4.6 mm i.d. as a stationary phase with a mobile phase consisting of acetonitrile- methanol-water (36:10:54, v/v/v), a flow rate of 1.5 ml/min and UV detection wavelength of 217 nm. Diazepam was used as internal standard. The standard calibration curve was linear over the concentration range of 100-2000 ng/ml (r=0.999). The equation of a linear regression line was y=8.05E-04+7.25E-04x with slope and intercept values of 0.0007 and 0.0008, respectively. The limit of detection was 12.25 ng/ml and the limit of quantification was set at 100 ng/ml. The intra- and inter-day assay coefficients of variation (CV) were 3.0+/-1.7 and 6.3+/-1.9%, respectively. The percentage of recovery was 102.1+/-5.6. Therefore, the HPLC method described here was simple, rapid and reproducible since it did not require extraction and evaporation processes in sample preparation, which will reduce time-consuming or expensive sample preparation.

Studies on complex formation between curcumin and Hg(II) ion by spectrophotometric method: a new approach to overcome peak overlap.

Complex formation between curcumin and Hg(II) ion MeOH/H2O (1: 1 v/v) was investigated and monitored by the spectrophotometric method. The absorption peak of unreacted curcumin which was close and overlapped with that of the complex, was removed by calculation using Microsoft Excel, thereby, allowing determination of the stoichiometry of the complex by the mole-ratio and the Job’s continuous variation methods. Both methods indicated that a 1:1 complex of curcumin and Hg(II) was formed in solution. The formation constant of the 1:1 Hg(II) complex was obtained from two methods, the equilibrium concentration calculation and the linear plot of Benesi-Hildebrand equation, as log K = 4.44 ± 0.16 and 4.83 ± 0.02, respectively. The structure is proposed as a tetrahedral complex of Hg(II) with one curcumin and two chloride ions as ligands.

Pharmacokinetic interaction between ketoconazole and praziquantel in healthy volunteers.

Background: Praziquantel, a broad‐spectrum anthelminthic, has been reported to undergo extensive first‐pass metabolism by cytochrome P450 (CYP) enzymes in vivo. Ketoconazole, a potent CYP3A4 inhibitor, is known to markedly increase plasma concentrations of many co‐administered drugs. However, no data are available on the potential pharmacokinetic drug interaction between ketoconazole and praziquantel in humans.

Effect of cytochrome P450 3A4 inhibitor ketoconazole on risperidone pharmacokinetics in healthy volunteers

What is known and objective:  Risperidone is an atypical antipsychotic agent used for the treatment of schizophrenia. It is mainly metabolized by human cytochrome P450 CYP2D6 and partly by CYP3A4 to 9‐hydroxyrisperidone. Ketoconazole is used as a CYP3A4 inhibitor probe for studying drug–drug interactions. We aim to investigate the effect of ketoconazole on the pharmacokinetics of risperidone in healthy male volunteers.