Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylbutazone (PBZ), a classic anti-inflammatory and prostaglandin-synthesis inhibitor drug, was used to determine the role of prostaglandins and other mediators on the development and perpetuation of the response to intraperitoneal Escherichia coli endotoxin administration. The PBZ (15 mg/kg of body weight) was administered IV 30 minutes after endotoxin administration and was repeated later at 6 and 12 hours at a dose of 10 mg/kg. A variety of evaluation measurements (hematologic, blood glucose, pyruvate, lactate and fibrinogen, serum beta-glucuronidase, prothrombin time, blood gases, hepatic glycogen, plasma esterase, capillary refill time, and rectal temperature) were utilized. Marked alterations were noted for all evaluators following endotoxin administration except for blood fibrinogen, prothrombin time, and plasma esterase activity. The PBZ therapy blocked the hemoconcentration, hyperglycemia, increased blood lactate, decreased bicarbonate, decreased blood pH, pyrexia, and prolonged capillary refill time responses associated with endotoxin administration. Despite the significant blocking effects of PBZ on endotoxin responses, the eventual survival rate was unaffected in these experiments.
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PMID:Therapeutic effect of phenylbutazone on experimental acute Escherichia coli endotoxemia in ponies. 678 19

Phenylbutazone (PBZ) was administered to six calves intravenously (i.v.) and orally at a dose rate of 4.4 mg/kg in a three-period cross-over study incorporating a placebo treatment to establish its pharmacokinetic and pharmacodynamic properties. Extravascular distribution was determined by measuring penetration into tissue chamber fluid in the absence of stimulation (transudate) and after stimulation of chamber tissue with the mild irritant carrageenan (exudate). PBZ pharmacokinetics after i.v. dosage was characterized by slow clearance (1.29 mL/kg/h), long-terminal half-life (53.4 h), low distribution volume (0.09 L/kg) and low concentrations in plasma of the metabolite oxyphenbutazone (OPBZ), confirming previously published data for adult cattle. After oral dosage bioavailability (F) was 66%. Passage into exudate was slow and limited, and penetration into transudate was even slower and more limited; area under curve values for plasma, exudate and transudate after i.v. dosage were 3604, 1117 and 766 microg h/mL and corresponding values after oral dosage were 2435, 647 and 486 microg h/mL. These concentrations were approximately 15-20 (plasma) and nine (exudate) times greater than those previously reported in horses (receiving the same dose rate of PBZ). In the horse, the lower concentrations had produced marked inhibition of eicosanoid synthesis and suppressed the inflammatory response. The higher concentrations in calves were insufficient to inhibit significantly exudate prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and beta-glucuronidase concentrations and exudate leucocyte numbers, serum thromboxane B2 (TxB2), and bradykinin-induced skin swelling. These differences from the horse might be the result of: (a) the presence in equine biological fluids of higher concentrations than in calves of the active PBZ metabolite, OPBZ; (b) a greater degree of binding of PBZ to plasma protein in calves; (c) species differences in the sensitivity to PBZ of the cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2 or; (d) a combination of these factors. To achieve clinical efficacy with single doses of PBZ in calves, higher dosages than 4.4 mg/kg will be probably required.
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PMID:Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. 1221 19