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Biomedical subjects

L B Mellett

Publications and source records attributed to L B Mellett.

32 records · Page 2Linked to original sources
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A method for the measurement of L-phenylalanine mustard in the mouse and dog by high-pressure liquid chromatography.

The distribution of L-phenylalanine mustard (L-PAM) was studied in dogs and mice by high-pressure liquid chromatography. Separation of L-PAM from its products of hydrolysis was accomplished with a mu-Bondapak C18 column, a solvent system composed of 2-methoxyethanol/0.1% acetic acid, and solvent programming with a step gradient. Complete separation was effected in less than 15 min. The half-life for disappearance of L-PAM from mouse blood was 41 min, whereas that from dog blood was 29 min. The monohydroxy derivative of L-PAM, L-MOH, disappeared from dog serum with a half-life of 32 min. L-MOH was not detectable in mouse tissue other than blood at times greater than 15 min after injection. In the dog at 4 hr after injection, the tissue/serum concentration ratios were greater than 1 for liver, spleen, intestine, skeletal muscle, urinary bladder and gallbladder. The concentration of L-PAM in the bile was approximately 500 times higher than that in serum.

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Inhibition of deamination of 14C-cytosine arabinoside (NSC-63878): a useful biologic assay for tetrahydrouridine (NSC-112907).

Inhibition of the deamination of 14C-cytosine arabinoside by two lots of tetrahydrouridine was studied in monkey serum. The average inhibition of deaminase activity was 78% for tetrahydrouridine lot AJ39 (1.0 muM) when the concentration of cytosine arabinoside ranged from 44.2 to 170.7 muM; under the same conditions tetrahydrouridine lot AJ22 inhibited deamination by an average of 68%. Apparent Ki values were 0.26 muM for AJ39 and 0.43 muM for AJ22. The assay may be used to check the relative biologic activity of various lots of tetrahydrouridine.

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PubMedDate not supplied

Tissue disposition of 3H-actinomycin D (NSC-3053) in the rat, monkey, and dog.

Tissue concentration of 3H-actinomycin D have been determined in the rat, monkey, and dog after an iv dose of 0.6 mg/m2 body surface area. The drug-tissue half-life was determined for various tissues of the rat, monkey, and dog. A mean drug-tissue half-life of 47 hours was calculated for the tissues of the dog. Exceptions were the testis and brain. Significant concentrations of 3H-actinomycin D failed to accumulate in the brain. Although testis drug concentrations were lower than most other tissues evaluated, the drug-tissue half-life was significantly greater than that of other tissues. In all species studied 3H-actinomycin D was rapidly depleted from serum after iv dosage, with concomitant accumulation of drug in the tissues. 3H-actinomycin D was excreted via the biliary and urinary routes in all species studied. No metabolites of 3H-actinomycin D were detected in the bile or urine of the rat, monkey, or dog with the methods employed. When expressed on a body weight basis, body surface area doses were more than threefold greater in the rat than in the dog. However, the average ratio of concentration X time values (rat C X T/dog C X T) for 11 different tissues of the rat and dog was only 1.3. The results strongly suggest that an equivalent dose of actinomycin D, with dosage based on a body surface area basis, results in nearly equal tissue-drug exposure for most tissues in various mammalian species.

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