Search PubMed⌕ Search

Biomedical subjects

L E Martin

Publications and source records attributed to L E Martin.

At least 55 records · Page 3Linked to original sources
PubMed1979

The determination of terbutaline in human plasma by selected ion monitoring of the t-butyldimethylsilyl ether.

A method is described for the quantitative determination of terbutaline in 2 ml human plasma. The drug is extracted from plasma as the terbutaline tetraphenylboron ion pair and determined by gas chromatography mass spectrometry of its t-butyldimethylsily ether. Salbutamol is used as internal standard. Quantification is achieved by selected ion monitoring of the ion m/z 482 derived from t-butyldimethylsilyl terbutaline and m/z 495 from t-butyldimethylsilyl salbutamol. The detection limit was estimated to be 250 pg terbutaline ml-1 plasma. The coefficient of variation at the level of 1 ng terbutaline ml-1 was 4.1% (n = 5).

Albuterol↗
PubMed1979

Bactericidal activity of fractionated granule contents from human polymorphonuclear leukocytes.

Proteins from human polymorphonuclear leukocyte granules were extracted with 0.2 M acetate, pH 4.0, and fractionated by Sephadex G-100 column chromatography. The fractions demonstrated selective bactericidal action against a deep rough cell wall mutant of Escherichia coli O111:B4 with rough lipopolysacharide and cell wall mutants of Salmonella typhimurium LT-2 with lipoplysacharide of Ra, Rc, Rd1, Rd2, and Re types. Smooth parent strains were most resistant to the bactericidal action. Fractions with greatest activity for the mutants were from valley regions (regions of low protein concentration) between three high protein peaks comprising myeloperoxidase, protease, and lysozyme, respectively. Susceptibility of the mutants to bactericidal action increased as sugar residues decreased in lipopolysaccharide. Gram-positive bacteria were susceptible to different fractions than were the gram-negative bacteria.

Blood Bactericidal Activity↗
PubMed1977

Relationship between plasma concentrations and pharmacological effects of labetalol.

In healthy normal subjects following the administration of labetalol the pharmacological effects were measured and compared with the plasma concentrations achieved. The inhibition of exercise induced tachycardia and inhibition of exercise induced increases in systolic pressure were significantly related to the administered dose of labetalol. Labetalol was rapidly absorbed from the gastrointestinal tract and peak plasma concentrations occurred two hours after oral administration. There was a linear correlation (r = 0.84) between the logarithm of the plasma concentration and the maximum inhibition of exercise tachycardia at two hours. After intravenous administration there was an immediate reduction in systolic and diastolic blood pressure with a concomitant small increase in heart rate. There was a rapid decline in the associated plasma concentration but the pharmacological effects were maintained in excess of two hours. Our findings are consistent with those of others who have studied the relationship between pharmacological events and plasma concentrations after single doses of other adrenoceptor blocking drugs.

Administration, Oral↗
PubMed1976

Quantitative determination of salbutamol in plasma, as either its trimethylsilyl or t-butyldimethylsilyl ether, using a stable isotope multiple ion recording technique.

Two methods are described for the determination of salbutamol in human plasma. The drug is extracted from the plasma as a salbutamol tetraphenylboron ion pair and determined by gas chromatography mass spectrometry. Trideuterio-salbutamol is used as an internal standard. In the first method an extensive purification procedure is used to separate salbutamol from plasma cholesterol which interferes in the assay. Salbutamol is then determined as its TMS-ether using a multiple ion recording technique to measure the intensity of the fragment ion m/e 369 and the ion m/e 372 from the TMS ether of trideuterio-salbutamol. The second method is based on the ion pair extraction of salbutamol into heptan-3-one and its determination by gas chromatography mass spectrometry as the t-butyldimethylsilyl ether. The base peak in the mass spectrum of the t-butyldimethylsilyl-salbutamol is an ion of m/e 495, which is of sufficiently high mass to distinguish it from any of the ions which arise from t butyldimethylsilyl-cholesterol. Six replicate analyses of plasma samples containing 1 ng salbutamol ml-1 were carried out using both methods. When the first method was used the mean value obtained was 1.3 ng ml-1 and the coefficient of variation was 17.7%. When the second method was used the mean value obtained was 0.95 ng ml-1 and the coefficient of variation was 10%. The second method is more rapid and therefore preferable for use in clinical pharmacological studies. This method has been used to determine the plasma salbutamol concentrations at varying times after either a 4 mg oral or a 200 mug intravenous dose of salbutamol to man.

Albuterol↗
PubMed1976

Metabolism of labetalol by animals and man.

1 The disposition and metabolism of labetalol and either 14C- or 3H-labetalol has been studied in mouse, rat, rabbit, dog and man. 2 Radiolabelled labetalol was administered orally at doses of 100 mg/kg to the mouse, up to 50 mg/kg to the rat and rabbit, 20 mg/kg to the dog and 200 mg to man. From measurements of the total plasma radioactivity it was shown that labetalol was well absorbed by all the species. When the measurements of plasma radioactivity and labetalol concentrations were compared, it was found labetaol had been extensively metabolized by the first-pass effect in rat, rabbit and man. Metabolism by this route occurred to a lesser extent in the dog. 3 Radiochemical analysis of the tissues from rats, rabbits and dogs showed that the highest concentrations of radioactivity were found in the lung, liver and kidney. Very little radioactivity was present in the brain. Over 99% of the radioactivity was cleared from the tissues by 7 d. When doses of up to 200 mg 14C-labetalol/kg were given to pregnant rats and 50 mg 14C-labetalol/kg to pregnant rabbits, autoradiographic and radiochemical analysis of the full-term foetuses showed that only small amounts of radioactivity were present in the foetus. 4 The mouse excreted 72%, the rate 48%, the rabbit 61%, the dog 66% and man 60% of the oral dose of radioactivity in the urine. Analysis of themouse and rat faeces showed that the remainder of the dose of radioactivity was excreted in the faeces. 5 Radiochemical analysis of the urine and faeces collected from rats and dogs after an intravenous dose of 1 mg 14C- and 3H-labetalol/kg showed that excretion of radioactivity occurred via both the kidney and bile. 6 An intravenous dose of 1 mg 3H-labetalol/kg to dog and 1 mg 'cold' labetalol/kg to man was not as extensively metabolized as a similar oral dose. 7 The percentage of the dose excreted in the urine as unchanged drug was 2% in the rabbit, 11% in the rat, 19% in the dog and up to 5% in man. The O-phenyl glucuronide was the major metabolite present in the mouse, rat, and rabbit urine. Dog and man also formed this metabolite, but to a lesser extent. A second glucuronide was the major metabolite present in dog urine. This was probably formed through conjugation of glucuronic acid was the secondary alcohol group of labetalol. The major metabolite present in human urine was an unidentified conjugate of labetalol. Minor metabolites of labetalol present in rat, rabbit and dog urine were hydroxylabetalol and its glucuronyl conjugate.

Administration, Oral↗
PubMed1976

Affinity of labetalol for ocular melanin.

1 The toxicity of labetalol has been studied in mice, rats, rabbits, and dogs, and reproductive studies have been carried out in rats and rabbits. Nothing was observed in any of these species to suggest that patients taking labetalol might be exposed to any toxic hazard. 2 During the reproductive studies 14C-labetalol was used to study placental transfer. Radioactivity was present in the uveal tract of the foetal eye. 3 Radioactive labetalol but not its metabolites was bound to the melanin pigment of the eye. This binding was reversible. It was not possible to saturate the melanin of the cat and dog eye even with prolonged dosing with labetalol. 4 Chloroquine, given orally at doses of 1.5-6 mg/kg/d for 4-7 weeks, produced changes in the cat retina. When oral doses of 20 mg labetalol/d were given to cats for 7 months, no oculotoxic effects were observed. 5 Detailed ophthalmological and histological examinations were carried out on the rats, rabbits, cats and dogs used in these studies. No changes indicative of oculotoxicity were observed. In the reproductive studies no effects were observed in the developing rat or rabbit eye, which could be consequent on the placental transfer of labetalol or its metabolites.

Administration, Oral↗
PubMed1975

Human placental transfer of AH8165.

The human placental transfer of AH8165 (0times50times9 mg/kg) was studied in ten patients undergoing elective Caesarean section. There was no adverse effect on foetal movement attributable to placental transfer of the neuromuscular blocking drug. Bioassay of umbilical vein blood indicated that little AH8165 crossed the placenta. Studies using 3HAH8165 in two patients undergoing termination hysterectomy demonstrated transfer of only minute amounts of radioactivity to the foetus.

Apgar Score↗