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Biomedical subjects

R M Welch

Publications and source records attributed to R M Welch.

At least 73 records · Page 4Linked to original sources

Codeine kinetics as determined by radioimmunoassay.

Radioimmunoassay (RIA) was used to determine several pharmacokinetic parameters of codeine in man, including the relative bioavailability after oral and intramuscular administration. The study followed a crossover design in 6 healthy, young (18 to 21 yr), male volunteers. Three subjects received 65 mg codeine phosphate orally in an analgesic mixture which also contained aspirin, phenacetin, and caffeine. At the same time a similar group received an equivalent dose of codeine phosphate in a single intramuscular injection. Two weeks later the study was repeated so that each group received the alternate treatment. Plasma samples were collected at various times after drug administration, and codeine concentrations were determined by a specific RIA procedure. The procedure can detect less than 50 pg of codeine. Following intramuscular administration, peak plasma concentrations (194 to 340 ng/ml) were observed between 0.25 to 1 hr; after oral dosing, peak codeine plasma concentrations (102 to 140 ng/ml) appeared within 0.75 to 1 hr. The mean plasma t1/2 and volume of distribution of codeine following intramuscular injection were 3.32 hr and 5.1 L/kg, respectively. Oral, relative to intramuscular, bioavailability of codeine, based on areas under the codeine plasma curves, was 42% to 71% (mean, 53%).

Administration, Oral↗

Determination of triprolidine in human plasma by quantitative TLC.

A chromatographic thin-layer fluorescence procedure, with a sensitivity limit of 0.8 ng/ml, is described for the quantitative analysis of triprolidine in human and rat plasma. Following the intravenous administration of 1 mg/kg of triprolidine to rats, the drug distributed rapidly into tissues and was eliminated from plasma with a half-life of 53 min. The method was used to determine the plasma triprolidine levels in 16 normal human volunteers following oral administration of 3.75 mg of triprolidine hydrochloride in 15 ml of a syrup. The drug obtained a mean peak plasma level of 8.2 ng/ml in 2 hr and was eliminated from the plasma with a half-life of 5 hr. Considerable individual variation was observed in the area under the plasma triprolidine level-time curve; values ranged from 19 to 163 ng hr/ml with a mean value of 75 ng hr/ml.

Administration, Oral↗

Effects of oxalic acid on availability of zinc from spinach leaves and zinc sulfate to rats.

Some effects of dietary oxalic acid on availability of zinc from organic and inorganic sources were assessed. Male rats fed zinc-deficient diets with and without added sodium oxalate were orally dosed once with either 65Zn-labeled spinach leaves or 65Zn-labeled zinc sulfate. Spinach plants (Spinacia oleracea, var. "Winter Bloomsdale") were grown in 65Zn-labeled nutrient solutions that contained 0.033, 0.131 or 0.262 ppm zinc. Increasing zinc supply to the plants increased zinc concentration in the leaves. Oxalic acid content in all leaves was about 7% dry weight. Dietary oxalate enhanced the availability of 65Zn from zinc sulfate, but had no effect on absorption and retention of 65Zn from spinach leaves. Regardless of dietary oxalate levels, absorption and retention of 65Zn was greater from spinach leaves than from zinc sulfate. We concluded that endogenous zinc in spinach leaves was readily available to zinc-deficient rats, and that dietary oxalate was not deleterious to zinc availability.

Absorption↗

Specific radioimmunoassays for codeine and morphine. Metabolism of codeine to morphine in the rat.

Specific antisera to morphine have been raised in response to immunization with a conjugate of N-carboxypropylnormorphine with bovine serum albumin (BSA). These antisera effectively distinguish changes in substituents at the 3 and 6 positions of the alkaloid, thus reducing cross-reactivity with codeine and morphine-3-glucuronide to negligible levels. The utility of these antisera has been illustrated by their application in radioimmunoassay procedures, along with similarly specific anti-codeine sera (Findlay et al., 1976) to a study of the biotransformation of codeine to morphine in the rat. After oral administration of codeine, serum levels of morphine were low, but significantly higher than codeine levels after 15 min., indicating rapid metabolism of codeine to morphine in this species.

Animals↗

Potentiation of the anti-inflammatory and analgesic activity of aspirin by caffeine in the rat.

Caffeine has been found to potentiate the acute anti-inflammatory activity of aspirin, indomethacin, and phenylbutazone, but not the activity of sodium salicylate or hydrocortisone, in the carrageenan pleurisy or hindlimb models of inflammation in the rat. The mobilization of inflammatory cells was not affected by aspirin in the presence or absence of caffeine. The mild analgesia produced by aspirin was confined to a hyperalgesic test in which this drug was able to reduce inflammation and concomitant hyperalgesia and thereby produce an "apparent" analgesic effect. This "apparent" analgesia produced by aspirin was potentiated by caffeine. The mechanism responsible for the potentiated anti-inflammatory and mild analgesic activity of aspirin remains unknown since caffeine did not alter the plasma salicylate levels or prostaglandin synthetase inhibition produced by aspirin.

Animals↗

Elimination of antipyrine from saliva as a measure of metabolism in man.

The salivary half-life of antipyrine was used as a convenient procedure for estimating the relative rates of drug metabolism in man. The concentration ratio of antipyrine in plasma and saliva was one over a 24-hr period following the oral or parenteral administration of the drug to man and rat. Phenobarbital, a known stimulator of drug metabolism in animals and man, increased markedly the elimination of antipyrine from saliva of rats, while SKF-525A, a potent inhibitor of drug metabolism, prolonged the elimination of antipyrine from rat saliva. In addition, the known sex difference in the metabolism of drugs in the rat was detected by measuring the elimination rate of antipyrine from saliva of male and female rats. The clinical application of the procedure indicated that a group of epileptic patients treated with anticonvulsants for more than 2 mo had a mean antipyrine salivary half-life of 4 hr, whereas a mean half-life of 13 hr was found in a group of normal volunteers. The results show that the elimination rate of antipyrine from saliva is a useful index of drug metabolism in animals and man.

Adolescent↗

Iron availability to rats from soybeans.

Experiments were carried out to determine the effects of endogenous phytic acid in soybean seeds (Glycine max, var. "Amsoy") on the bioavailability of 59Fe to iron-depleted rats. Soybean plants were grown in nutrient solutions labeled with 59Fe supplied at either 0.4 or 1.0 ppm iron in solution. Immature and mature soybean seeds were harvested and fed to male rats as a single dose. The phytic acid content of the immature and mature seeds averaged 0.61 and 1.71% dry weight, respectively. Varying the nutrient solution iron concentration in the mature soybean seeds. When the 59Fe-labeled seeds were fed to iron-deficient rats, 59Fe from the mature seeds was more available than that from immature seeds even though the mature seeds contained approximately three times as much phytic acid. Autoclaving the mature seeds did not affect the absorption of 59Fe by rats from the seeds. Immature soybean seeds contained much more insoluble 59Fe than did mature soybean seeds. It was concluded that the directly correlated to the phytate content of the seeds; also immature soybean seeds apparently contain a factor or factors (other than phytic acid) that depresses iron availability.

Animal Nutritional Physiological Phenomena↗

Vanadium Uptake by Plants: Absorption Kinetics and the Effects of pH, Metabolic Inhibitors, and Other Anions and Cations.

The kinetics of vanadium absorption by excised barley (Hordeum vulgare L., cv. Eire) roots were investigated with respect to ionic species of V in solution, time and concentration dependence, Ca sensitivity, and interaction with various anions, cations, and pH levels. The role of metabolism in V absorption was also studied using anaerobic treatment (N(2) gas) and chemical inhibitors (NaN(3), KCN, or 2,4-dinitrophenol). Approximately one-third of the labeled V initially taken up by excised roots was desorbed to a constant level after 45 min in unlabeled V solutions. The rate of absorption of labeled V from 5 mum NH(4)VO(3) solutions containing 0.5 mm CaSO(4) was constant for at least 3 hours. Omission of Ca resulted in a 72% reduction in V uptake when compared to controls with 0.5 mm CaSO(4). The rate of uptake of V was highest at pH 4 but dropped to a very low level at pH 10. It was relatively constant between the pH levels of 5 and 8 at which the VO(3) (-) ion is the predominant ionic species in solution. The rate of absorption of V was followed as a function of concentrations from 0.5 to 100 mum NH(4)VO(3). It was found to be a linear function of concentration and did not follow saturation kinetics. Absorption experiments carried out with labeled V from either N(a)VO(3) or NH(4)VO(3) sources gave similar results. No anion studied (i.e. HPO(4) (2-), HAsO(4) (2-), MoO(4) (2-), SeO(4) (2-), SeO(3) (2-), CrO(4) (2-), BO(3) (3-), No(3) (-), and Cl(-)) interfered appreciably (i.e. less than 30% inhibition) with the absorption of labeled V. Anaerobic treatment of absorption solution with N(2) gas did not inhibit V absorption by excised roots. The results obtained using chemical inhibitors were not consistent. It was concluded that V is not actively absorbed by excised barley roots.

Journal Article↗

Vanadium and plant nutrition: the growth of lettuce (lactuca sativa L.) and tomato (lycopersicon esculentum mill.) plants in nutrient solutions low in vanadium.

Lettuce (Lactuca sativa L.) and tomato (Lycopersicon esculentum Mill.) plants were grown in purified nutrient solutions with and without the addition of 50 nanograms per milliliter V. These experiments showed that lettuce and tomato plants can be grown to maturity on nutrient solutions containing less than 0.04 nanogram per milliliter V with tissue concentrations of less than 2 to 18 nanograms per gram V. Growth and dry matter yield were comparable to those of plants grown on nutrient solutions containing 50 nanograms per milliliter with tissue levels of V from 117 to 418 nanograms per gram. Thus if V is an essential element for lettuce and tomato plants, the adequate tissue level would be less than 2 nanograms per gram V derivable from a growth medium containing less than 0.04 nanogram per milliliter V.

Journal Article↗