| Kinase Assay: |
| Drug Metab Lett. 2014;8(2):135-44. | | The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacokinetics of CYP3A probe drug buspirone in rats.[Pubmed: 25434398] | Aconitine (AC), an active/toxic alkaloid from Aconitum species, is commonly present in Traditional Chinese Medicine (TCM) prescriptions because of the great effectiveness of Aconitum for the treatment of rheumatoid arthritis, cardiovascular diseases, and tumors in clinic. Buspirone (BP) is a sensitive CYP3A probe drug that is administered through oral/intravenous routes as recommended by the U.S. Food and Drug Administration.
METHODS AND RESULTS:
This study aims to investigate the influences of AC (0.125 mg/kg, oral) on first-pass (intestinal and hepatic) CYP3A activity by using oral BP as the probe in rats. The pharmacokinetics of oral buspirone hydrochloride at different doses (12.5, 25, and 50 mg/kg) were conducted. The pharmacokinetics of oral BP in rats pretreated with single dose or multiple doses (7-day) of AC were investigated. The plasma concentrations of BP and its major metabolites [1-(2-pyrimidinyl)piperazine (1-PP) and 6'-hydroxybuspirone (6'-OH-BP)] were determined. The formation ratios of 1-PP and 6'-OH-BP from BP (AUC0-∞ of 1-PP/AUC0-∞ of BP and AUC0-∞ of 6'-OH-BP/AUC0-∞ of BP values) showed no alternation when the dose of BP changed. Single dose of AC decreased the AUC0-∞ of BP by 53% but increased the formation ratio of 6'-OH-BP by 74% (P<0.05). Multiple AC exposure increased the AUC0-∞ of BP by 110%, and the formation ratios of 1-PP and 6'-OH-BP from BP were increased by 229% and decreased by 95%, respectively (P<0.05).
CONCLUSIONS:
Conclusively, single/multiple AC exposure did not alter the first-pass CYP3A activity when using oral BP as probe in rats. Nevertheless, multiple AC exposure had markedly changed the production of BP metabolites. |
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| Animal Research: |
| J Cardiovasc Pharmacol. 1981 Jan-Feb;3(1):87-100. | | Hemodynamic and arrhythmogenic effects of aconitine applied to the left atria of anesthetized cats. Effects of amiodarone and atropine.[Pubmed: 6160357] |
METHODS AND RESULTS:
The arrhythmogenic and hemodynamic effects of 0.04% Aconitine solution applied locally to the left atria of cats and the effects of amiodarone (10 mg/kg) and atropine (0.2 mg/kg) on the responses to Aconitine were investigated. Cats were anesthetized with sodium pentobarbital. The left atrial and limb lead electrocardiograms and the arterial pressure were recorded. Cardiac output was determined with the thermo dilution technique. Aconitine nitrate induced dysrhythmias lasting for a mean of 111 min. Atrial fibrillation occurred in 47% of the animals. A long-lasting (at least 3 hr) cardiodepressant action was seen in response to Aconitine. Pretreatment with atropine largely prevented the hemodynamic effects of Aconitine and prevented fibrillation. However, mean maximum atrial rates recorded during successive 5 min intervals were similar in control and atropine-treated animals. Amiodarone suppressed dysrhythmias in both atropine-treated and nontreated animals at a dose which exerted only minimal cardiodepression.
CONCLUSIONS:
The method described for evaluating potential activity against supraventricular dysrhythmias in the cat is relatively simple, reproducible, and suitable for statistical analyses. Aconitine appears to exert a long-lasting cholinergic action which may be involved in the genesis of Aconitine-induced atrial fibrillation. |
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| Structure Identification: |
| J Pharm Sci. 2014 Nov;103(11):3602-10. | | An in vitro and in vivo comparison of solid and liquid-oil cores in transdermal aconitine nanocarriers.[Pubmed: 25187419] |
METHODS AND RESULTS:
This study compared transdermal Aconitine delivery using solid lipid nanoparticles (SLN) and microemulsion (ME) vehicles. Aconitine-loaded SLN and ME were formulated with the same surfactant, cosurfactant, and water content, with an equal amount of oil matrix (ATO 888 for SLN and ethyl oleate for ME). These nanosized formulations (70-90 nm) showed suitable pH values and satisfactory skin tissue biocompatibility. SLN contained a higher concentration of smaller nanoparticles, compared with that in ME. Neither of the nanocarriers penetrated across excised skin in their intact form. In vitro transdermal delivery studies found that transdermal Aconitine flux was lower from SLN than from ME (p < 0.05), but skin Aconitine deposition was higher using SLN (p < 0.05). Fluorescence-activated cell sorting indicated that in vitro uptake of fluorescently labeled SLN by human immortalized keratinocyte (HaCaT) cells was greater than that of ME, indicating that a transcellular pathway may contribute to cutaneous drug absorption more effectively from SLN.
CONCLUSIONS:
In vivo studies found that these formulations could loosen stratum corneum layers and increase skin surface crannies, which may also enhance transdermal Aconitine delivery. SLN produced a more sustained Aconitine release, indicating that compared with ME, this transdermal delivery vehicle may reduce the toxicity of this drug. | | Zhong Yao Cai. 2014 Feb;37(2):284-7. | | [Pharmacokinetic study of six aconitine alkaloids in aconiti lateralis radix praeparata in beagle dogs].[Pubmed: 25095352] | To study the pharmacokinetics characteristics of six Aconitum alkaloids Aconitine (AC), mesAconitine (MA), hypAconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in beagle dogs.
METHODS AND RESULTS:
An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids in beagle dog plasma after oral administration of Aconiti Lateralis Radix Praeparata decoction. UPLC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. Sample preparation was performed with solid-phase extraction(SPE) on a 3 mL HLB cartridge before the analysis. The separation was applied on a Waters C8 column (100 mm x 2.1 mm, 1.7 microm) and a gradient elution of methanol and 0.2% formic acid-water was used as mobile phase. The pharmacokinetic parameters were calculated by the results of the analysis through the DAS 2. 1 software (Drug and Statistics for Windows).
The results showed that the fitting model for the six Aconitum alkaloids was the one-compartment model pharmacokinetics.
CONCLUSIONS:
The method is successfully used for the pharmacokinetic evaluation of the six Aconitum alkaloids in beagle dog plasma, it can help monitor the ADME/Tox process when taking Aconiti Lateralis Radix Praeparata by observing the pharmacokinetic process. The results provide a good reference for clinical treatment and safe application of Aconiti Lateralis Radix Praeparata. |
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