Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new butazolidin research articles will be listed here shortly after becoming available to us.
Related Sponsors
Medical research on butazolidin
J Pharm Sci. 2008 Aug 4;
Yang W, Li Y, Cheng Y, Wu Q, Wen L, Xu T
The interactions between phenylbutazone, a well-established nonsteroidal anti-inflammatory drug, with different generations of poly(amidoamine) (PAMAM) dendrimers, have been investigated by aqueous solubility, two dimensional nuclear Overhauser effect spectroscopy (2D-NOESY) and isothermal titration calorimetry (ITC) studies. Solubility results showed that PAMAM dendrimers significantly enhanced the aqueous solubility of phenylbutazone and the solubilization was much influenced by dendrimer concentration, generation, surface function group and pH value. The 2D-NOESY spectra clearly showed that there were several kinds of cross-peaks from NOE interactions between the protons of phenylbutazone and the protons in interior cavities of both generation 6 and generation 3 PAMAM dendrimers. The solubility, 2D-NOESY results and ITC analysis suggest that encapsulation and electrostatic interaction together caused the solubility enhancement of phenylbutazone. The new techniques such as 2D-NOESY and ITC used in this study are useful tools in investigating the interactions between dendrimers and guest molecules. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
Eur J Pharm Sci. 2008 Sep 2; 35(1-2): 127-35
Van Eerdenbrugh B, Froyen L, Van Humbeeck J, Martens JA, Augustijns P, Van den Mooter G
d-alpha-Tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized nanosuspensions (25wt%, relative to the drug weight) were produced by media milling for 9 model drug compounds [cinnarizine, griseofulvin, indomethacin, itraconazole, loviride, mebendazole, naproxen, phenylbutazone and phenytoin]. After 3 months of storage at room temperature, Ostwald ripening occurred in all of the samples, except for indomethacin. Whereas lowering the temperature could slow down the ripening, it markedly increased upon storage at 40 degrees C. As for ripening, settling generally became more pronounced at 40 degrees C compared to 4 degrees C. As the nanosuspensions were afflicted by Ostwald ripening and settling, we explored nanosuspension drying as a strategy to circumvent these stability issues. Spray-drying and freeze-drying were evaluated for nanosuspensions and coarse reference suspensions of the compounds. Nanoparticle agglomeration could be visually observed in all of the powders. To evaluate the effect of agglomeration on the key characteristic of drug nanocrystals (i.e. rapid dissolution), dissolution experiments were performed under poor sink conditions. It was found that the compounds could be categorized into 3 groups: (i) compounds for which it was impossible to differentiate between coarse and nanosized products (griseofulvin, mebendazole, naproxen), (ii) compounds that gave clear differences in dissolution profiles between the nanosized and the coarse products, but for which drying of the nanosuspensions did not decrease the dissolution performance of the product (indomethacin, loviride, phenytoin) and (iii) compounds that showed differences between coarse and nanosized products, but for which drying of the nanosuspensions resulted in a significant decrease of the dissolution rate (cinnarizine, itraconazole, phenylbutazone). To gain insight on the influence of the drug compound characteristics on the dissolution of the dried products, the dissolution behavior of the compounds of the second and the third group was linked to the compound's characteristics. It was found that compounds with a more hydrophobic surface resulted in agglomerates which were harder to disintegrate, for which dissolution was compromised upon drying. The same was found for compounds having higher logP values.
J Zoo Wildl Med. 2008 Jun; 39(2): 188-200
Bechert U, Christensen JM, Nguyen C, Neelkant R, Bendas E
The pharmacokinetic parameters of phenylbutazone were determined in 18 elephants (Loxodonta africana and Elephas maximus) after single-dose oral administration of 2, 3, and 4 mg/kg phenylbutazone, as well as multiple-dose administrations with a 4-wk washout period between trials. After administration of 2 mg/kg phenylbutazone, mean serum concentrations peaked in approximately 7.5 hr at 4.3 +/- 2.02 microg/ml and 9.7 hr at 7.1 +/- 2.36 microg/ml for African and Asian elephants, respectively, while 3 mg/kg dosages resulted in peak serum concentrations of 7.2 +/- 4.06 microg/ml in 8.4 hr and 12.1 +/- 3.13 microg/ml in 14 hr. The harmonic mean half-life was long, ranging between 13 and 15 hr and 39 and 45 hr for African and Asian elephants, respectively. There was evidence of enterohepatic cycling of phenylbutazone in Asian elephants. Significant differences (P < 0.0001) in pharmacokinetic values occurred between African and Asian elephants for clearance (27.9 and 7.6 ml/hr/kg, respectively), terminal half-life (15.0 and 38.7 hr, respectively), and mean residence time (22.5 and 55.5 hr, respectively) using 2-mg/kg dosages as an example. This suggests that different treatment regimens for Asian and African elephants should be used. There were no apparent gender differences in these parameters for either elephant species.
Retina. 2008 Jul 14;
Pastor J, Del Nozal MJ, Zamarron E, García M
PURPOSE:: To determine, in vitro, the solubility in silicone oil (SO) of triamcinolone acetonide, dexamethasone, and some nonsteroideal antiinflammatory drugs including phenylbutazone and nabumetone. METHODS:: Antiinflammatory drugs were initially dissolved in organic solvents (chloroform or diethyl ether). The solubilized drugs were then added to 1,000 centipoise purified SO to yield final concentrations that were therapeutically relevant. The degree of solubilization was judged by the transparency of the final mixture. The kinetics of phenylbutazone diffusion from SO into water were measured for 30 days by derivative spectrophotometry. RESULTS:: Most of the tested drugs, including triamcinolone acetonide, were not soluble in SO. Only phenylbutazone and nabumetone, each at 80 mug/mL, were soluble in SO. The release of phenylbutazone from SO into water over a 30 day period followed zero order kinetics during the first 15 days. CONCLUSION:: Triamcinolone acetonide and most other antiinflammatory drugs tested are not soluble in SO. This fact must be taken into consideration when using these drugs in combination with SO.
Toxicology. 2008 Aug 19; 250(1): 15-26
Uehara T, Hirode M, Ono A, Kiyosawa N, Omura K, Shimizu T, Mizukawa Y, Miyagishima T, Nagao T, Urushidani T
For assessing carcinogenicity in animals, it is difficult and costly, an alternative strategy has been desired. We explored the possibility of applying a toxicogenomics approach by using comprehensive gene expression data in rat liver treated with various compounds. As prototypic non-genotoxic hepatocarcinogens, thioacetamide (TAA) and methapyrilene (MP) were selected and 349 commonly changed genes were extracted by statistical analysis. Taking both compounds as positive with six compounds, acetaminophen, aspirin, phenylbutazone, rifampicin, alpha-naphthylisothiocyanate, and amiodarone as negative, prediction analysis of microarray (PAM) was performed. By training and 10-fold cross validation, a classifier containing 112 probe sets that gave an overall success rate of 95% was obtained. The validity of the present discriminator was checked for 30 chemicals. The PAM score showed characteristic time-dependent increases by treatment with several non-genotoxic hepatocarcinogens, including TAA, MP, coumarin, ethionine and WY-14643, while almost all of the non-carcinogenic samples were correctly predicted. Measurement of hepatic glutathione content suggested that MP and TAA cause glutathione depletion followed by a protective increase, but the protective response is exhausted during repeated administration. Therefore, the presently obtained PAM classifier could predict potential non-genotoxic hepatocarcinogenesis within 24h after single dose and the inevitable pseudo-positives could be eliminated by checking data of repeated administrations up to 28 days. Tests for carcinogenicity using rats takes at least 2 years, while the present work suggests the possibility of lowering the time to 28 days with high precision, at least for a category of non-genotoxic hepatocarcinogens causing oxidative stress.
Anti-inflammatory activity of indanyltetrazole derivatives.
Pak J Pharm Sci. 2008 Jul; 21(3): 295-8
Bepary S, Das BK, Bachar SC, Kundu JK, Shamsur Rouf AS, Datta BK
A number of indanyl tetrazolederivatives namely 5-(6'-chloroindan-1'-yl)tetrazole (CIT), 5-(6'-bromoindan-1'-yl)tetrazole (BIT), 5-(6'-chloroindan-1'-yl)methyltetrazole (CIMT), 5-(6'-bromoindan-1'-yl)methyl-tetrazole (BIMT) were evaluated for the anti-inflammatory activity in carragennan induced rat paw edema in Swiss albino Wister rats for 24-hour period at the dose of 100 mg/kg of body weight by intraperitoneal route where phenylbutazone (PBZ) was used as the standard. All of these compounds exhibited inhibition on rat paw edema with peak actions observed following 3 hours after administration. Moreover, compounds CIMT and BIMT were further evaluated at dose of 50 mg/kg of body weight. Among the compounds, CIMT showed higher activity than others and was very close to standard phenylbutazone.
Amino acid positions 69-132 of UGT1A9 are involved in the C-glucuronidation of phenylbutazone.
Arch Biochem Biophys. 2008 Jun 24;
Nishiyama T, Fujishima M, Masuda Y, Izawa T, Ohnuma T, Ogura K, Hiratsuka A
Phenylbutazone (PB) is known to be biotransformed to its O- and C-glucuronide. Recently, we reported that PB C-glucuronide formation is catalyzed by UGT1A9. Interestingly, despite UGT1A8 sharing high amino acid sequence identity with UGT1A9, UGT1A8 had no PB C-glucuronidating activity. In the present study, we constructed eight UGT1A9/UGT1A8 chimeras and evaluated which region is important for PB C-glucuronide formation. All of the chimeras and UGT1A8 and UGT1A9 had 7-hydroxy-(4-trifluoromethyl)coumarin (HFC) O-glucuronidating activity. The K(m) values for HFC glucuronidation of UGT1A8, UGT1A9 and their chimeras were divided into two types, UGT1A8 type (high K(m)) and UGT1A9 type (low K(m)), and these types were determined according to whether their amino acids at positions 69-132 were those of UGT1A8 or UGT1A9. Likewise, PB O-glucuronidating activity was also detected by all of the chimeras, and their K(m) values were divided into two types. On the contrary, PB C-glucuronidating activity was detected by UGT1A9((1-132))/1A8((133-286)), UGT1A9((1-212))/1A8((213-286)), UGT1A8((1-68))/1A9((69-286)), and UGT1A8((1-68))/1A9((69-132))/1A8((133-286)) chimeras. The region 1A9((69-132)) was common among chimeras having PB C-glucuronidating activity. Of interest is that UGT1A9((1-68))/1A8((69-132))/1A9((133-286)) had lost PB C-glucuronidation activity, but retained activities of PB and HFC O-glucuronidation. These results strongly suggested that amino acid positions 69-132 of UGT1A9 are responsible for chemoselectivity for PB and affinity to substrates such as PB and HFC.
Vet Ther. 2008; 9(2): 122-7
Longhofer SL, Reinemeyer CR, Radecki SV
The efficacy of top-dress antiinflammatory drugs ultimately depends on a patient's willingness to consume treated feed. The current study compares the palatability of two phenylbutazone top-dress formulations (Equipalazone Powder, Dechra Pharmaceuticals, and Pro-Dynam, VetXX, Ltd.) and a suxibuzone top-dress formulation (Danilon Equidos, Janssen Animal Health). Results of a three-period, crossover study on 18 healthy horses showed that Pro-Dynam was significantly less palatable, with significantly less consumption of treated feed compared with either Equipalazone Powder or Danilon Equidos. There was no statistically significant difference in terms of consumption of treated feed and palatability scores between Equipalazone Powder and Danilon Equidos.
Biochem Pharmacol. 2008 Jul 15; 76(2): 249-57
Kerdpin O, Knights KM, Elliot DJ, Miners JO
In order to gain insights into the renal and hepatic glucuronidation of frusemide (FSM), this study: (i) characterised the kinetics of FSM glucuronidation by human liver microsomes (HLM) and human kidney cortical- (HKCM) and medullary- (HKMM) microsomes, and (ii) identified the human UDP-glucuronosyltransferase enzyme(s) involved in this pathway. HLM, HKCM and HLMM efficiently glucuronidated FSM. FSM glucuronide (FSMG) formation followed Michaelis-Menten kinetics in all tissues. While the mean K(m) for FSMG formation by HKMM (386 +/- 68 microM) was lower than the K(m) values for HLM (988 +/- 271 microM) and HKCM (704 +/- 278 microM), mean V(max)/K(m) values were comparable for the three tissues. A panel of recombinant UGT enzymes was screened for the capacity to glucuronidate FSM. UGT 1A1, 1A3, 1A6, 1A7, 1A9, 1A10 and 2B7 metabolised FSM. Of the renally and hepatically expressed enzymes, comparison of kinetic parameters suggests a predominant role of UGT1A9 in FSM glucuronidation, although UGT1A1 may also contribute to FSMG formation by HLM. Consistent with these observations, the UGT1A selective inhibitors phenylbutazone and sulfinpyrazone decreased FSMG formation by HLM, HKCM and HKMM by 60-80%, whereas the UGT2B7 selective inhibitor fluconazole reduced FSM glucuronidation by < or =20%. The ability of HKCM and HKMM to form FSMG supports the proposition that the kidney is the main organ involved in FSM glucuronidation in vivo, although a role for hepatic metabolism remains a possibility in renal dysfunction. The data further demonstrate the potential importance of both the medulla and cortex in renal drug metabolism and detoxification.
Drug Metab Dispos. 2008 Aug; 36(8): 1562-9
Liu HX, Liu Y, Zhang JW, Li W, Liu HT, Yang L
Glucuronidation is an important pathway in the metabolism of protocatechuic aldehyde (3,4-dihydroxybenzaldehyde, PAL). However, the metabolites and primary UDP-glucuronosyltransferase (UGT) isozymes responsible for PAL glucuronidation remain to be determined in human. Here, we characterized PAL glucuronidation by human liver microsomes (HLMs), human intestine microsomes (HIMs), and 12 recombinant UGT (rUGT) isozymes to identify what kinds of metabolites are present and which human UGT isozymes are involved. Two metabolites (M-1 and M-2) were detected in reactions catalyzed by HLMs, HIMs, rUGT1A6, and rUGT1A9 and were identified as monoglucuronides by liquid chromatography-mass spectrometry. A kinetic study showed that PAL glucuronidation by rUGT1A6, rUGT1A9, HIMs, and HLMs followed Michaelis-Menten kinetics. The K(m) values of HLMs, HIMs, rUGT1A6, and rUGT1A9 for PAL glucuronidation were as follows: 432.7 +/- 24.5, 626.9 +/- 49.2, 367.5 +/- 25.1, and 379.9 +/- 42.5 microM for M-1 and 336.7 +/- 15.3, 494.3 +/- 48.7, 211.4 +/- 13.4, and 238.5 +/- 26.2 microM for M-2, respectively. The PAL glucuronidation activity was significantly correlated with UGT1A6 activity rather than with UGT1A9 activity from 15 individual HLMs. A chemical inhibition study showed that the IC(50) for phenylbutazone inhibition of PAL glucuronidation was similar in HLMs (61.9 +/- 7.9 microM) compared with rUGT1A6 (45.3 +/- 7.7 microM). In contrast, androsterone inhibited rUGT1A9-catalyzed and HLM-catalyzed PAL glucuronidation with IC(50) values of 27.1 +/- 3.8 and > 500 microM, respectively. In combination, we identified UGT1A6 as the major isozyme responsible for PAL glucuronidation in HLMs.