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Biomedical subjects

M C Meyer

Publications and source records attributed to M C Meyer.

At least 73 records · Page 4Linked to original sources
PubMed1981

High-performance liquid chromatographic assay of tolbutamide and carboxytolbutamide in human plasma.

A high-performance liquid chromatographic method was developed for the simultaneous measurement of tolbutamide and its major metabolite, carboxytolbutamide, in plasma. The assay involves the ether extraction of 1 ml of plasma, using chlorpropamide and an internal standard. The extract is dried, the residue is taken up in acetonitrile, and 5 micro l is injected into a reversed-phase column. The mobile phase consisted of 35% acetonitrile and 65% 0.05 M phosphoric acid buffer (pH 3.9). A fixed-wavelength detector was set at 254 nm. The sensitivity limits for the tolbutamide and carboxytolbutamide assay were 2 and 0.1 microgram/ml, respectively. The ratio of carboxytolbutamide to tolbutamide in plasma obtained from a subject given a 500-mg tolbutamide tablet was 1:20.

Chlorpropamide↗
PubMed1981

The pharmacokinetics of trichlormethiazide in hypertensive patients with normal and compromised renal function.

The pharmacokinetics of trichlormethiazide (TCZ) was studied in twelve patients after a single 4 mg dose. Seven patients had normal renal function with creatinine clearance greater than 90 ml/min. Five patients had compromised renal function with creatinine clearances averaging 48 +/- 29 ml/min. The TCZ plasma half life and area under the plasma concentration-time curve (AUC) were significantly greater in patients with impaired function, compared to patients with normal renal function. There were no significant differences between the two patient groups in terms of either rate of drug absorption or total urinary recovery of unchanged drug. Furthermore, there was no correlation between peak drug levels or AUC and renal excretion of water or electrolytes.

Female↗
PubMed1981

Hexoprenaline pharmacokinetics in pregnant and nonpregnant sheep.

Hexoprenaline, a beta 2-sympathomimetic agent, is used to suppress uterine contractions in the treatment of premature labor. However, little is known regarding the potential of this drug to undergo placental transfer or whether the pregnant state alters any of the pharmacokinetic parameters. Using sheep as a model, intravenous doses of 14C-hexoprenaline were administered to pregnant and non-pregnant animals. Measurable levels of radioactivity did not appear in fetal blood samples. After intravenous bolus administration, blood concentrations in the ewe could be fitted by a triexponential curve characteristic of a three-compartment pharmacokinetic model. Following intravenous infusion, a biexponential curve described the decline in blood concentrations. Mean terminal half lives for total radioactivity ranged from 2.5 to 4.2 hours. The pregnant animals tended to exhibit smaller apparent volumes of distribution and lower values for total body clearance, normalized to body weight, compared to non-pregnant sheep.

Animals↗
PubMed1980

Bioavailability of microsize and ultramicrosize griseofulvin products in man.

The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The "high-dose" study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The "low-dose" study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p > 0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p < 0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dosage studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.

Adult↗
PubMed1980

Differentiation of Rhizobium japonicum strain derivatives by antibiotic sensitivity patterns, lectin binding, and utilization of biochemicals.

Several strains of Rhizobium japonicum have been reported to consist of mixtures of stable derivativess having distinct colony morphologies and physiological characteristics. We isolated derivatives from strains of R. japonicum and systematically compared them with previously isolated derivatives with respect to the utilization of biochemicals, antibiotic sensitivity, and soyben lectin binding. With the exception of a pair of derivatives from 3Ilb110, one of which utilized pyruvate and one of which did not, sibling derivatives had essentially identical biochemical utilization patterns. The sibling derivatives of parental strains 3Ilb110 and 3Ilb140 exhibited marked variation in their sensitivities to several antibiotics, including gentamicin, sul famethoxazole, and tetracycline. Compared with the derivative with small colony morphology, derivatives with large colony morphology were in general more sensitive to these antibiotics. With one exception, the binding of soybean lectin to the derivatives was quantitatively the same as that to the parental strain. The anomaly was 110-Y which, in contrast to its parental strain and sibling derivatives, failed to bind detectable amounts of the lectin. 110-Y, as well as all the other derivatives and parental strains, nodulated Disoy soybean.

Anti-Bacterial Agents↗
PubMed1980

A multiple-dose study of sustained-release theophylline and aminophylline.

This study evaluated the relative bioavailability of a sustained-release capsule of theophylline, an elixir of theophylline, and a sustained-release tablet of aminophylline. Twelve healthy, nonsmoking, adult male subjects received nine doses of each of the three products in a crossover study conducted over a ten-day period. Each dosage form contained approximately 250 mg of theophylline and was administered every eight hours. Concentrations of theophylline in the plasma at steady state demonstrated the equivalence of the three dosage forms in terms of the percent of drug absorbed, including the tablet which had exhibited reduced bioavailability in an earlier single-dose study of only five subjects. The steady-state average concentrations of theopylline in the plasma were 9.8 micrograms/ml, 10.3 micrograms/ml and 10.8 micrograms/ml for the tablet, capsulse, and elixir, respectively. The areas under the curves of the plasma level vs time for the three dosage forms were within 9 percent of each other. These data indicate that a significant reduction in fluctuations of the plasma level of theophylline was achieved with the two sustained-release dosage forms, compared to the elixir.

Adult↗
PubMed1980

Evaluation of enzyme immunoassay, radioassay, and radioimmunoassay of serum methotrexate, as compared with liquid chromatography.

We evaluated three commonly used clinical methods for measuring serum methotrexate: enzyme immunoassay (EMIT), radioassay, and radioimmunoassay. Because potentially interfering compounds can be resolved by liquid chromatography, this method was selected as the comparison method. Patients' serum samples, taken during 24 h after 6-h high-dose infusions, contained methotrexate in concentrations ranging from 10(-7) to 10(-4) mol/L. Chromatograms revealed substantial amounts of 7-hydroxymethotrexate in all samples, actually exceeding methotrexate by 12 and 24 h. Nevertheless, analysis of variance revealed no significant differences in results by any of the four methods, nor did results by the three test methods differ significantly after being adjusted by analysis of covariance with liquid chromatography as the covariate. Evidently any of the four techniques is suitable for monitoring serum methotrexate for 24 h after high-dose therapy.

Adolescent↗
PubMed1980

Pharmacokinetics of propylthiouracil upon p.o. administration in man.

A pharmacokinetic analysis of propylthiouracil (PTU) plasma concentration versus time data for twelve euthyroid subjects was performed using the NONLIN computer program. The plasma concentration-time curves were best described by a one-compartment open model. PTU was administered to fasted subjects as a single 150-mg peroral dose. Venous blood samples were taken for a period of 8 hrs, and the concentration of unmetabolized PTU was determined by a new specific high-pressure liquid chromatographic procedure. Estimates of pharmacokinetic parameters generated in the study were compared with corresponding parameters reported in the literature.

Administration, Oral↗
PubMed1979

Bioavailability of chlorothiazide tablets in humans.

A urinary excretion bioavailability study was conducted in 12 healthy male subjects to evaluate three 250-mg and three 500-mg chlorothiazide tablet products. The study was a crossover design, and urine samples were collected 1, 2, 3, 4, 6, 8, 12, and 24 hr after administration of each dose. The resulting data were statistically analyzed for significant differences in cumulative percent of dose excreted at each sampling time, total drug recovery after 24 hr, maximum excretion rate, and time of maximum excretion rate. No statistically significant differences were found between the three 250-mg tablets tested. The urinary drug recovery after administration of one of the 500-mg products was significantly (p less than 0.05) lower than that from the other two 500-mg tablets. The total mean recovery from each product ranged from only 11 to 20%, indicating that in general chlorothiazide was not well absorbed following oral administration. Attempts at correlating the urinary excretion data with the dissolution rate determinations were not successful.

Adult↗
PubMed1979

High-pressure liquid chromatographic assay for griseofulvin in plasma.

A high-pressure liquid chromatographic procedure was developed for griseofulvin assay in human plasma. The method utilized warfarin as an internal standard and easily quantitated griseofulvin plasma levels as low as 0.10 micrograms/ml. The method was compared to two fluorometric assay methods and was more specific for griseofulvin. Assay of 6-demethylgriseofulvin isolated from human urine demonstrated that this material was not responsible for the interferences apparent in the fluorometric procedures.

Biotransformation↗
PubMed1978

Relative bioavailability of meprobamate tablets in humans.

The relative bioavailability of 400-mg meprobamate tablets manufactured by 11 different firms was evaluated in two groups of healthy male subjects. Each group of six subjects received a reference standard product and five test products given at 1-week intervals. Plasma meprobamate concentrations at 1, 2, 3, 4, 6, 8, 10, 24, and 32 hr after dosing were determined using a GLC assay. Analysis of variance of the plasma level--time profiles revealed no statistically significant differences between any of the products in terms of plasma levels at the various sample times, time of peak plasma level, peak plasma level, and area under the plasma level--time curve. It was concluded that the 11 400-mg products could be considered bioequivalent.

Adult↗
PubMed1978

Bioavailability of sulfadiazine solutions, suspensions, and tablets in humans.

A four-way crossover sulfadiazine bioavailability study was conducted in 16 normal healthy male volunteers. The subjects were divided into groups of eight. Each group received four different oral dosage forms of sulfadiazine at 1-week intervals: a solution as a reference, a suspension, and two different tablets. All dosage forms were equivalent to 500 mg of sulfadiazine. Blood samples were obtained at 0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 25.0, 33.0, and 49.0 hr. Analysis of variance indicated no statistically significant difference (p more than 0.05) between the dosage forms in terms of area under the plasma level--time curve, peak plasma concentration, and time of peak plasma concentration. In both groups, there were differences between products at isolated sampling times. It was concluded that the four tablet formulations of sulfadiazine exhibited bioavailability characteristics equivalent to those of the solution and the suspension.

Administration, Oral↗
PubMed1977

Meprobamate.

Explore the source record for details and available documents.

Biological Availability↗
PubMed1977

Estimation of drug dosage regimens with a pharmacokinetic slide rule.

A pharmacokinetic slide rule to facilitate the computations based on relatively simple pharmacokinetic principles involved in the development of individualized drug dosage regimens is described. The calculations are based on the assumption that the body can be conceived as a one-compartment open model with drug elimination proceeding by apparent first-order kinetics. Examples are presented (1) to illustrate the clinical application of a slide rule to compute the time-course of drug in the body, (2) to calculate steady-state maximum and minimum levels, and accumulation during multiple dosage and (3) to estimate appropriate maintenance doses and intravenous infusion rates.

Kinetics↗
PubMed1976

Binding of salicylate and sulfathiazole by whole blood constituents.

The binding of salicylic acid and sulfathiazole to bovine whole blood, plasma proteins, and purified albumin fraction was investigated using a dynamic dialysis system. The binding profiles for salicylic acid were quite similar in bovine plasma and 4% bovine serum albumin. In contrast, the binding of sulfathiazole was significantly greater in the plasma than in solutions of fraction V bovine serum albumin. Data from dynamic dialysis binding studies of the compounds, conducted in whole blood and suspended erythrocyte systems, did not lend themselves to analysis by classical methods. Hemolysis and alteration in the nature of the protein binding sites during the binding studies were shown to be factors that could explain the unusual binding observed in the whole blood system.

Animals↗