Edward J. Van Loon

Metabolism of chlorpheniramine-3H by the rat and dog☆

Abstract Chlorpheniramine-3H is rapidly and completely absorbed from the gastrointestinal tract of the rat and the dog. About 70–80 per cent of the administered radioactivity contained in a single acute dose is excreted in urine and feces in 4 days with most of the radioactivity being recovered in urine in 24 hr. When rats, but not dogs, are pretreated with nonradioactive chlorpheniramine and then given the labeled compound, the recovery of tritium in urine and feces is essentially complete in 4 days. Maximum radioactivity in blood in both species was observed 30–60 min after oral drug administration and the blood level fell to half its maximum value in 24 hr. Radioactivity was detected in rat tissues 15 min after dosing and reached peak levels in 30–60 min. About 50 per cent of an oral dose of chlorpheniramine-3H is excreted in rat bile in 24 hr. N-dealkylation is a major pathway for the metabolism of chlorpheniramine-3H in both the rat and the dog. Didesmethylchlorpheniramine is the major dealkylated metabolite detected in urine of both species after the doses of chlorpheniramine investigated. Only 1–3 per cent of chlorpheniramine-3H is excreted unchanged in the urine.

Isolation and characterization of glucuronic acid conjugates of chlorpromazine in human urine.

Summary Four polar, water-soluble metabolites of chlorpromazine were separated from urine by use of a cation exchange resin. These were shown to be glucuronides by release of free glucuronic acid and less polar, ether-extractable phenothiazines as a result of β-glucuronidase hydrolysis. Presence of enolic functions in these released phenothiazines was shown by their extractability from an acidic medium. Results strongly suggest hydroxylation of chlorpromazine and subsequent conjugation with glucuronic acid as an important route of chlorpromazine metabolism and detoxification in man.

Determination of N′,N′-anhydrobis (β-hydroxyethyl)-biguanide hydrochloride in urine

Summary A differential spectrophotometric method for the urinary determination of N′,N′ -anhydrobis( β -hydroxyethyl)biguanide hydrochloride (ABOB) is described. Following preliminary purification by precipitation of contaminating material with barium hydroxide plus zinc sulfate and ion-exchange chromatography, a portion of the sample is treated with bromine water to alter the ABOB molecule so that it does not absorb in the ultraviolet region of the spectrum. The concentration of ABOB is then determined by reading a second portion of the sample against the bromine-treated sample. Each urine specimen therefore serves as its own blank.

Effect of thyromimetic agents on oxygen uptake of rat heart and liver.

Summary L-3:5:3′-triiodothyronine and 3:5:3′-triiodothyroacetic acid significantly increased total body oxygen consumption of intact and thyroidectomized rats. L-3:5:3′-triiodothyronine and triiodothyroacetic acid also significantly increased in vitro oxygen uptake of heart and liver slices; however, the heart did not respond to a greater degree than the liver. Thyroxamine failed to increase total body oxygen consumption or Qo2 of liver; however, the Qo2 value of the heart was significantly increased.