J. J. Burns

Observations on the antirheumatic and physiologic effects of phenylbutazone (butazolidin) and some comparisons with cortisone

Abstract 1. 1. Phenylbutazone exhibits antirheumatic effects in rheumatoid arthritis which are comparable to those shown by cortisone and corticotropin. 2. 2. Like cortisone and corticotropin the drug causes urinary retention of sodium, chloride and water, and may reactivate peptic ulcers; but unlike cortisone it does not affect the excretion of potassium nor does it cause eosinopenia or increased ketosteroid excretion. It is concluded that the action of phenylbutazone is not mediated, directly or indirectly, through the adrenal cortex. 3. 3. During phenylbutazone therapy there is often a fall in red cell count, hemoglobin and hematocrit which is primarily the result of hemodilution and not of depression of the hematopoietic system. 4. 4. Plasma levels of phenylbutazone approach a limiting concentration as dosage is increased. This limiting concentration varies widely from patient to patient. Most subjects achieve plasma levels on 400 to 600 mg. daily that are only slightly lower than when 800 mg. are given.

The transmission of meperidine across the human placenta

Much of Apgars research during the early 1950s focused on the effects of maternal anesthesia on the newborn child; she and other investigators asked whether anesthetic agents crossed the placenta from mother to fetus, and if so, whether the drugs endangered the baby. In this case, they found that meperidine (Demerol) did cross the placental barrier, but did not depress the respiration of the newborn.

Observations on G-25671, A Phenylbutazone Analogue (4-(phenylthioethyl) −1,2-diphenyl 3,5-pyrazolidinedione).∗:

Summary and Conclusions 1. Observations were made on the physiological behavior of a compound in which the butyl side chain of phenylbutazone was replaced by a phenyl-thioethyl group. 2. Rate of biotransformation of this compound in man was greatly accelerated, with a biologic half life of only 3 hours compared to 70 hours for phenylbutazone. Such rapid disappearance might have some advantage in minimizing toxic manifestations but would pose the problem of maintaining therapeutic levels since the drug would have to be given at relatively frequent levels. 3. Like phenylbutazone, G-25671 exerted distinct antirheumatic effects but produced little or no sodium retention and consequently no hemodilution. These observations show that the antirheumatic and sodium-retaining properties in the phenylbutazone series may be dissociated. 4. The drug has a more marked uricosuric effect than phenylbutazone.

Effect of a phenylbutazone analog (4-[phenylthioethyl]-1, 2-diphenyl 3, 5-pyrazolidinedione) on urate clearance and other discrete renal functions in gouty subjects; evaluation as uricosuric agent.

(From the Departments of Medicine, The Mount Sinai Hospital, and Columbia University College of Physicians and Surgeons, New York, N. Y.; Research Serzice, Third (New York University) Medical Division, Goldwater Memorial Hospital, New York, N. Y.; and the Laboratory of Chemical Pharmacology, National Heart Institute, National Institutes of Health, U. S. Public Health Service, Department of Health, Education and Welfare, Bethesda, Md.)

The control of prothrombin activity with tromexan therapy

D IFFICULTIES in the control of the hypothrombinemic effect of dicumarol@ in the treatment of thromboembolic diseases have led to the investigation of other coumarin derivatives. With one of these, tromexan@)t (3,3’-carboxymethylenbis [4-hydroxycoumarin] ethyl ester), the therapeutic effects take place more rapidly after administration of the drug and disappear more rapidly after discontinuance of the drug than is the case with dicumarol. These characteristics of tromexan are potential advantages in that they might be expected to permit more predictable control of induced hypoprothrombinemia. There was some confirmation of the early expectations1-5 but this has not been borne out in later studies.6*7 Previous works indicates that tromexan is rapidly and completely absorbed from the gastrointestinal tract, compared to the slow and sometimes incomplete absorption of dicumarol. Its biotransformation is rapid, the plasma concentration falling at an average rate of 25 per cent per hour, compared to dicumarol which falls at an average rate of about 40 per cent per day.g As with dicumarol the rate of metabolic transformation of tromexan varies widely in different subjects. The rapid disappearance of tromexan from the body is accompanied with a rapid return of the prothrombin time to pretreatment levels on discontinuing therapy. After a single dose the drug has almost disappeared from the body before the prothrombin response becomes evident, eight to twelve hours after drug administration.1 Single daily doses of the drug