Effect of single and multiple treatments with phenylbutazone in normal and adjuvant-induced polyarthritic rats

DiPasquale, G.; Rassaert, Charles L.; Welaj, P; Gingold, James L.

doi:10.1007/bf02027159

Cited by 6 publications

(2 citation statements)

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“…A similar increase in the relative excretion of OPBZ during acute inflammation has been reported in the rat, which was considered to result from altered metabolism secondary to inflammation and not from a difference in renal function (Baake et al. 1974;DiPasquale et a/.. 1975).…”

Section: Discussionmentioning

confidence: 63%

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

Mills

Auer

1996

Vet Pharm & Therapeutics

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The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n = 5) or 4.4 mg/kg (n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases (P < 0.05) in total body clearance (CLB; 29.2 +/- 3.9 vs. 43.8 +/- 8.1 mL/ h.kg) and the volume of distribution, calculated by area (Vd(area); 0.18+/- 0.05 vs. 0.25 +/- 0.03 L/kg) or at steady-state (Vd(SS); 0.17 +/- 0.04 vs. 0.25 +/- 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly (P < 0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.

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Section: Discussionmentioning

confidence: 63%

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

Mills

Auer

1996

Vet Pharm & Therapeutics

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“…In recent years inhibition of drug metabolism, i.e., the mixed function oxidase (MFO) system, in rats affected with experimentally-induced inflammatory diseases has generated considerable interest. Rats made polyarthritic by the injection of Mycobacterium in oil (Freund's adjuvant) have impaired hepatic (Morton & Chatfield, 1970;Whitehouse & Beck, 1973; DiPasquale, Rassaert, Welaj & Gingold, 1975;Cawthorne, Palmer & Green, 1976) as well as pulmonary MFO metabolizing capacity (Carlson & Ciaccio, 1975). Arthritis in rats induced by Mycoplasma arthritidus (Cawthorne et al, 1976) or 6-sulphonanilamidoindazole (Swingle, Chang & Erikson, 1978) was associated with reduced metabolism of drugs.…”

Section: Introductionmentioning

confidence: 99%

DEPRESSION OF DRUG METABOLISM IN THE MOUSE BY A COMBINATION OF Mycobacterium butyricum AND ANAESTHETICS

Barbieri

Ciaccio

1979

British J Pharmacology

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Subcutaneous injection of Mycobacterium butyricum suspended in mineral oil into the mouse hind paw caused an oedematous local inflammation. Hind paw swelling was maximum 5 days after injection and was still apparent at day 30. Drug metabolism in vivo (as monitored by ketamine‐ or pentobarbitone‐induced sleeping times) was not affected by the inflammatory disease. However, administration of ketamine or pentobarbitone at day 1 led to significantly elevated sleeping times when the mice showing local inflammation were retested at day 5 with the anaesthetics. Indomethacin inhibited hind paw oedema in the mouse but did not affect ketzmine‐Mycobacter‐ium butyricum‐induced depression of drug metabolism. Prolongation of ketamine‐induced anaesthesia by combination with Mycobacterium butyricum at day 5 correlated with the degree of hind paw inflammation at this time. The data suggest that anaesthetics (i.e., ketamine and pentobarbitone) may sensitize hepatic membranes to the effect of Mycobacterium butyricum or some toxic compound elaborated during the active phase of inflammation.

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Klinisch-therapeutische Aspekte der experimentellen Adjuvansarthritis

Schmidt

1986

Der Rheumatismus

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Effect of single and multiple treatments with phenylbutazone in normal and adjuvant-induced polyarthritic rats

Cited by 6 publications

References 20 publications

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

DEPRESSION OF DRUG METABOLISM IN THE MOUSE BY A COMBINATION OF Mycobacterium butyricum AND ANAESTHETICS

Klinisch-therapeutische Aspekte der experimentellen Adjuvansarthritis

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