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Biomedical subjects

W D Mason

Publications and source records attributed to W D Mason.

At least 19 recordsLinked to original sources
PubMed1996

High-performance liquid chromatographic determination of phenylephrine and its conjugates in human plasma using solid-phase extraction and electrochemical detection.

An HPLC method for the determination of phenylephrine and its conjugates in human plasma was developed and validated. The method for quantitation involved extraction of diluted plasma (subject to hydrolysis with beta-glucuronidase for 30 min with 500 units of enzyme per 0.1 ml of plasma at 37 degrees C for the conjugates) on solid-phase weak cation-exchange cartridges followed by elution of the analyte and the internal standard (ethylnorphenylephrine) with 5% triethylamine in methanol. Analysis was carried out on a 15 cm ODS stationary phase using ion-pair reversed-phase chromatography. An electrochemical detector operated at + 1.15 V vs. Ag/AgCl was employed for detection. The standard curves were linear in the range 1.0-50.0 ng ml-1 for phenylephrine and 25.0-500.0 ng ml-1 for phenylephrine obtained from its conjugates. The limit of quantitation was 2.0 ng ml-1 (RSD = 17%) and 25.0 ng ml-1 (RSD = 18%), respectively. Acceptable accuracy and precision were obtained during intra- and inter-batch analyses for both the assays.

Adrenergic alpha-Agonists↗
PubMed1995

Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers.

Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. A sensitive flourimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been developed to study the pharmacokinetics of selegiline. This method quantitates selegiline as low as 0.25 ng ml-1. The pharmacokinetics and relative bioavailability of selegiline were investigated in healthy volunteers following oral administration of 10 mg tablet or solution. A half-life of approximately 70 min was observed following the administration of either dosage form. Although the two dosage forms exhibited a lag time, the absorption was rapid and peak plasma concentrations were observed between 30 and 45 min for the solution and 30 and 90 min for the tablets. Statistically no significant difference was found between Cmax, Tmax, AUC0-infinity and MRT between the two dosage forms. Negligible renal clearance was found in both groups, but apparent oral plasma clearance was comparatively high and indicates rapid elimination of selegiline from the body.

Adult↗
PubMed1994

The pharmacokinetics and absolute bioavailability of selegiline in the dog.

Selegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. Currently no pharmacokinetic data are available for selegiline in the literature, mainly due to lack of analytical methods that can measure concentrations below 10 ng mL-1 in plasma. A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been developed to measure selegiline in plasma as low as 0.25 ng mL-1. The pharmacokinetics of selegiline were investigated following intravenous and oral administration to four female mongrel dogs. Each dog received 1 mg kg-1 selegiline in solution via gavage or by an intravenous route separated by one week. The mean terminal half-life, volume of distribution of the central compartment, and systemic clearance of selegiline were 60.24 +/- 9.56 min, 6.56 +/- 0.56 L kg-1, and 159.91 +/- 19.28 mL min-1 kg-1, respectively. After oral administration selegiline appeared to be absorbed rapidly with a tmax and Cmax of 25 +/- 5.8 min and 5.2 +/- 1.36 ng mL-1, respectively. The absolute bioavailability of selegiline in the dog was 8.51 +/- 3.31%.

Absorption↗
PubMed1994

An enzymatic assay for the MAO-B inhibitor selegiline in plasma.

A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been described. The procedure measures the inhibition of MAO activity produced by the addition of selegiline extracted from human plasma. This method uses the substrate kynuramine which is converted by MAO to the product 4-hydroxyquinoline which fluoresces in alkaline solution. Human plasma (500 microliters) containing different concentrations of selegiline was deproteinized and extracted with ethyl acetate-butyl chloride. After reconstitution with 200 microliters phosphate buffer, 50 microliters of rat brain homogenate was added to study the MAO-B inhibition. Selegiline metabolites, amphetamine and methamphetamine (50 ng ml-1), and desmethylselegiline (20 ng ml-1), showed no inhibitory effect on MAO-B inhibition. Selegiline concentrations as low as 0.25 ng ml-1 can be detected. The standard curve was linear from 125 pg (0.25 ng ml-1) to 4000 pg (8.0 ng ml-1) in the incubation tube. This method should be helpful to determine pharmacokinetic parameters of selegiline after i.v. or oral dosing.

Amphetamine↗
PubMed1994

Determination of m-hydroxymandelic acid, m-hydroxyphenylglycol and their conjugates in human plasma using liquid chromatography with electrochemical detection.

An LC method for the analysis of m-hydroxymandelic acid (MHMA) and m-hydroxyphenylglycol (MHPG) and their conjugates in human plasma was developed and validated. The method for the quantitation involved extraction of acidified plasma (subject to hydrolysis with beta-glucuronidase for 120 min with 500 units of enzyme/0.25 ml of plasma at 37 degrees C for the conjugates) with an organic phase (methyl-tert-butyl ether). Analysis of MHMA, MHPG and the internal standard (3-hydroxy-4-methoxymandelic acid) was carried out on an ODS stationary phase: 100 x 4.6 mm, 5 mu followed by a 75 x 4.6 mm, 3 mu using 1% acetonitrile in 0.1 M acetic acid as the mobile phase. An electrochemical detector operated at +1.15 V vs Ag/AgCl was employed for the detection. The standard curves were linear in the range of 10.0-250.0 ng ml-1 for MHMA and 5.0-125.0 ng ml-1 for MHPG. The limit of quantitation was 10.0 ng ml-1 for MHMA and MHPG. Acceptable accuracy and precision were obtained during the intra-batch and inter-batch analysis for both the assays.

Chromatography, High Pressure Liquid↗
PubMed1992

High-performance liquid chromatographic method for the determination of tris(hydroxymethyl)aminomethane (tromethamine) in human plasma.

Determination of tris(hydroxymethyl)aminomethane (tromethamine) in human plasma involved derivatization of the amino and hydroxyl groups with a ultraviolet-absorbing chromophore followed by extraction into an organic phase. Reversed-phase high-performance liquid chromatography with gradient elution was used for the separation of the analyte from the internal standard (2,3-butanediol). The assay was linear in the range 1.0-1000.0 micrograms/ml of plasma and the coefficient of variation varied between 9.6 and 16.3% whereas the accuracy varied between 90 and 108%. The limit of detection for the assay was 0.282 micrograms/ml. Stability of tris(hydroxymethyl)aminomethane in human plasma frozen at -20 degrees C was studied over a period of three month and the data indicated no significant change.

Chromatography, High Pressure Liquid↗
PubMed1992

Method for the determination of diphenhydramine in rabbit whole blood by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection in conjunction with gas chromatography (GC) with mass selective detection (MSD).

An HPLC/GC-MSD method for the determination of diphenhydramine in rabbit whole blood has been developed and validated. This method is based on a liquid-liquid extraction and reversed-phase chromatography with ultraviolet absorbance detection monitored at 258 nm. HPLC eluant fractions containing diphenhydramine and the internal standard, orphenadrine, were collected, reextracted, then subjected to GC-MSD analysis. Whole blood was utilized, thereby decreasing the required sample volume and increasing the sensitivity of the assay. Diphenhydramine concentrations can be quantitated over a range of 1 to 1000 ng/ml whole blood.

Animals↗
PubMed1991

A dose-ranging study of the pharmacokinetics of codeine phosphate following intravenous administration to rats.

The linearity of the pharmacokinetics of codeine was examined in male Sprague-Dawley rats given iv bolus doses of 1, 1.5, 3, and 4 mg/kg of codeine phosphate. Codeine and morphine were determined in serial blood samples utilizing HPLC with electrochemical detection. Codeine exhibits characteristics consistent with a two-compartment pharmacokinetic model. The kinetics of codeine are linear in the iv dose range 1-4 mg/kg. The ratio AUCmorphine:AUCcodeine increases disproportionately with increasing doses of codeine.

Animals↗
PubMed1991

The pharmacokinetics of aspirin in rats and the effect of buffer.

Aspirin (acetylsalicyclic acid) was administered to rats intravenously, orally, and intraintestinally at different doses or in different dosage forms. The distribution and elimination kinetics of aspirin in rats following intravenous administration were best described by a two-compartmental open system and were dose independent up to 15 mg/kg. The terminal elimination half-life following intravenous dosing (10 mg/kg) was 3.36 +/- 0.85 min (n = 15) with the clearance being 8.40 +/- 1.24 L/(kg.hr). Intravenous distribution and elimination kinetics of aspirin in rats were not influenced by an orally administered buffered solution with a buffer capacity of 0.933 mEq ANC (acid neutralizing capacity) per kg of body weight. However, this orally buffered solution did change the gastrointestinal absorption kinetics of aspirin in rats. The absolute bioavailable dose of aspirin was 56.6 +/- 10.4% (n = 6) following its administration in an unbuffered solution while it was only 31.8 +/- 8.0% (n = 6) following administration in the buffered solution. The corresponding values of the absolute bioavailable doses were 43.4 +/- 3.7% and 25.5 +/- 1.8% following intraintestinal administration. The lower systemic availability of aspirin in the presence of buffer is attributed to a greater fraction of the administered dose becoming available for absorption from the intestine where the extraction efficiency is higher than that in the stomach.

Administration, Oral↗
PubMed1990

Plasma codeine and morphine concentrations after a single oral dose of codeine phosphate.

Plasma concentrations of codeine and its O-demethylated metabolite morphine were determined, by a sensitive and specific high performance liquid chromatography (HPLC) method, following a single oral dose of 60 mg codeine phosphate. Ten healthy volunteers received a single dose of 60 mg codeine phosphate. The plasma concentrations were analyzed for codeine and morphine at the 0.5, 1, 3, and 6 hours postdosing. The mean peak codeine plasma concentrations and tmax (time to reach maximum plasma codeine concentrations) were 88.1 ng/mL and 1.2 hours. Mean maximum concentrations of metabolically produced morphine was 2.7 +/- 0.6 ng/mL. The mean ratio of areas under the plasma concentration-time curves for morphine and codeine was 0.027. Thus, free morphine represented only about 2.7 +/- 1.8% of the free codeine area in each case.

Administration, Oral↗
PubMed1989

Interaction between propranolol and propafenone in healthy volunteers.

The effects of propafenone on the pharmacokinetics and pharmacodynamics of propranolol were evaluated in 12 healthy male subjects. Both propafenone and propranolol were each administered alone for one week followed by concomitant administration for an additional week. Blood samples, obtained at steady-state, were analyzed for propafenone and its two metabolites as well as for propranolol and 4-hydroxypropranolol. Left ventricular function, exercise performance and electrocardiographic intervals were assessed. Coadministration of propranolol did not produce any significant change in propafenone kinetics including peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination rate constant (t1/2), mean steady-state plasma concentration (Css), or area under the concentration vs time curves. However, concomitant propafenone administration significantly increased Cmax (83%), Tmax (55%), t1/2 (30%), and Css (213%) which were accompanied by significant decreases in plasma levels of 4-hydroxy-propranolol. Propafenone and propranolol significantly reduced supine systolic and diastolic blood pressure by 2.5 to 15.4%. The combination did not reduce diastolic blood pressure further (64.0 +/- 2.8 to 59.7 +/- 1.7 mmHg) nor did it produce a supplemental reduction in heart rate (12% reduction with propranolol, 10% reduction with concomitant administration). Propranolol, but not propafenone, significantly decreased end-diastolic volume index (13%), stroke volume index (15%), and velocity of circumferential fiber shortening (19%). The combination did not cause any further changes in echocardiographic measurements. Electrocardiographic intervals were not altered by either drug use alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Determination of propranolol and 4-hydroxypropranolol in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed to determine the levels of propranolol and its major metabolite, 4-hydroxypropranolol, in human plasma. The limits of determination are 10 ng ml-1 of propranolol and 5 ng ml-1 of 4-hydroxypropranolol using a 0.5-ml plasma sample. The stability of plasma samples stored at -30 degrees C for up to 2 months was also tested. No stabilising antioxidants were added to the samples.

Chemical Phenomena↗
PubMed1987

Plasma and saliva propafenone concentrations at steady state.

Twenty-four healthy male subjects were administered 300 mg of propafenone every 8 h for 6 d in each of two phases that were separated by 2 d. Plasma samples were collected during the approach to steady state for each phase, and plasma and saliva samples were collected frequently at steady state. Both plasma and saliva propafenone were assayed by a specific HPLC method. Two estimates of elimination half-life (t1/2), mean steady-state concentration (CPss), time to maximal concentration (tmax), and maximal concentration (CPmax) were estimated for each subject. Also mean steady-state saliva concentrations (CSss), time to maximal saliva concentration (tSmax), and maximal saliva concentrations (CSmax) were estimated. A large intersubject variance in both t1/2 and CPss were observed in the 24 subjects, with the t1/2 values ranging from 2.1 to 27.2 h and the CPss values from 0.3 to 3.03 microgram/mL. Each subject was quite consistent for the two phases, suggesting a relatively low intrasubject variance for propafenone kinetics. A histogram shows most subjects to have t1/2 values between 2 and 10 h, with diminishing numbers of subjects at greater t1/2 values rather than a bimodal distribution. Saliva concentrations ranged from 12 to 72% of the corresponding plasma concentrations, being 24.7 +/- 11.1% of the simultaneously collected plasma sample overall (mean +/- SD). a significant (p less than 0.001) positive correlation exists between CPss and CSss.

Adult↗
PubMed1987

Between-lot and within-lot comparisons of bioavailability of macrocrystalline nitrofurantoin capsules.

Comparative bioavailability studies should be designed and the resulting data evaluated based on estimates of both intersubject and intrasubject variances in the kinetic parameters for the particular drug products(s) being studied. This report presents the results of two comparative bioavailability studies. In the first study, three production lots of macrocrystalline nitrofurantoin capsules (Macrodantin) were compared in 21 subjects, and in the second study, capsules from one production lot were administered to 21 different subjects on three occasions. Both model-independent kinetic parameters for urinary excretion and a one-compartment model with zero-order absorption were used to evaluate both the rate and the extent of bioavailability. Overall the results showed a very low variance between and within production lots and a relatively large intersubject variance in the rate and extent of absorption.

Biological Availability↗
PubMed1987

Food increases the bioavailability of propafenone.

The effect of food intake on the bioavailability of propafenone, a new antiarrhythmic agent, was evaluated by comparing its kinetics in 24 healthy volunteers in a fasted state and after a standard breakfast. With food, the maximum plasma drug concentration was reached earlier and was significantly increased. When data from 'slow' metabolizers were excluded, there was an average increase of 147% in the area under the concentration-time curve (AUCo) following the standard breakfast. There was a significant correlation (r = 0.946) between [(AUCo fed - AUCo fasted)/AUCo fasted] and propafenone intrinsic clearance in the fasted state. Food intake, however, does not appear to affect the bioavailability of propafenone in 'slow' metabolizers. Patients should be advised to take propafenone in a constant relationship to food to assure consistent bioavailability.

Adult↗
PubMed1985

The pharmacokinetics of alpha-methyldopa in dogs.

alpha-Methyldopa was intraarterially and orally administered to dogs at two dose levels in a randomized complete crossover design. The appearance of secondary peaks in the plasma concentration-time profiles indicated the presence of enterohepatically recycled methyldopa. This was established by the absence of a secondary peak following readministration of a dose after biliary cannulation and the detection of methyldopa in the bile of a cannulated dog. Enterohepatic recirculation was estimated to account for a mean of 16.2% of the area under the plasma concentration-time profile after intraarterial administration. Total systemic clearance, defined as the sum of elimination by all routes from the general circulation of the administered dose, and corrected for enterohepatic recirculation, averaged (+/- SD) 99.4 +/- 24.6 ml/min in the dog. An extended average apparent terminal half-life of 6.0 +/- 5.2 hr was exhibited after oral administration compared to an average half-life of 3.1 +/- 1.8 hr following intraarterial administration. Elimination kinetics were linear in the dose range studied. Oral plasma concentration data suggest that the apparent bioavailable fraction may be dose dependent.

Administration, Oral↗
PubMed1984

Comparative aspirin absorption kinetics after administration of sodium- and potassium-containing buffered solutions.

Twelve fasting normal volunteers received three aspirin dosage forms in a single 325-mg dose in a complete crossover study; the plasma aspirin and salicylic acid levels and the urine salicylic acid and salicyluric acid levels were measured over 10 h. The three dosage forms included an unbuffered tablet and two effervescent solutions, one with sodium bicarbonate-citrate buffer and the other with potassium bicarbonate-citrate buffer. A significantly faster absorption rate was observed with the sodium bicarbonate-citrate buffer, when compared with the potassium bicarbonate-citrate buffer and the unbuffered tablets, which were equivalent. These differences were attributed primarily to gastric emptying rate differences. Urine pH and salicylate renal clearance were significantly affected by the single dose of antacid buffer. The area under the curve and urine accumulation comparisons suggested that approximately 25% more aspirin reaches the general circulation intact after administration of the unbuffered tablet than the two solutions, but that the total salicylate absorbed is equivalent for all three dosage forms. This difference in aspirin bioavailability is probably due to the fact that the two buffered solutions are predominantly absorbed through the intestine, in which presystemic hydrolysis occurs, whereas a significant portion of the tablet dose is absorbed through the gastric mucosa.

Adult↗