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Biomedical subjects

R J Lewis

Publications and source records attributed to R J Lewis.

At least 289 records · Page 16Linked to original sources
PubMed1975

Warfarin-phenylbutazone interaction in man: a long term multiple dose study.

The effect of phenylbutazone on the disposition of warfarin was studied in a subject given warfarin daily for one month. During concomitant phenylbutazone administration, the total plasma warfarin concentration declined from 4.2 to 2.0 mg/L. In contrast, the unbound warfarin plasma concentration rose from 0.020 to 0.033 mg/L. The plasma concentration and daily urinary excretion of 7-hydroxywarfarin fell during phenylbutazone administration. Warfarin is administered as a racemate. Exclusive to and the major metabolic route of the more potent S-isomer is 7-hydroxylation. It is concluded that inhibition of S-warfarin metabolism can help explain the increased anticoagulation seen when phenylbutazone is added to the dosage regimen of a patient stabilized on warfarin.

Adult↗
PubMed1975

Canine glomerulonephritis: prevalence in dogs submitted at random for euthanasia.

The kidneys from 71 stray dogs submitted for euthanasia were examined by fluorescence microscopy (IF) for evidence of immunecomplex glomerulonephritis (GN) and by histology for evidence of renal pathology. Dogs were divided into three groups according to estimated age: less than one year old (A), adult (B) and aged (C). IgG deposits were found in 0/31 dogs in group A, 6/20 in group B and 10/20 in group C. Diffuse proliferative GN was evident in 0/31, 5/19 and 7/15 dogs in group A, B and C respectively. One dog in group B and two in group C had histological signs of membranous nephropathy. No definite correlation between results of IF and clinical findings were noted and in the aged group the correlation between results of IF and histopathology was poor. These results serve to show that GN may be more common in dogs than previously recognized and that pathological changes may be always accompanied by clinical nephritis.

Animals↗
PubMed1974

Warfarin. Stereochemical aspects of its metabolism and the interaction with phenylbutazone.

An examination of the metabolic fate of the R and the S isomers of warfarin revealed that the two isomers were metabolized by different routes. R warfarin was oxidized to 6-hydroxywarfarin and was reduced to the (R,S) warfarin alcohol. In contrast, S warfarin was oxidized to 7-hydroxywarfarin and was reduced to the (S,S) warfarin alcohol. S warfarin was also oxidized to 6-hydroxywarfarin. These observations suggested that interactions between warfarin and other drugs might be manifest stereo-specifically, i.e., have a different effect on the isomers of warfarin, so a series of experiments were conducted with each isomer of warfarin, before and after phenylbutazone. The plasma clearance of S warfarin was slowed from 3.1 to 1.1% per h in one subject and from 2.3 to 1.6% per h in another. In contrast, the clearance of R warfarin was increased from 1.5 to 3.0% per h and from 0.9 to 1.6% per h in two subjects after phenylbutazone. The rate of clearance of racemic warfarin was unaffected by phenylbutazone; the depression of the rate of clearance of the S isomer masked the stimulation of the clearance of the R isomer. Since S warfarin is five times more potent an anticoagulant than R warfarin, it is concluded that inhibition of the metabolism of S warfarin provides one mechanism for the augmented anticoagulation which follows phenylbutazone.

Blood Coagulation↗