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Biomedical subjects

M C Meyer

Publications and source records attributed to M C Meyer.

At least 55 records · Page 3Linked to original sources
PubMed1989

Gas chromatographic-mass spectrometric analysis of plasma nifedipine.

A gas chromatographic-mass spectrometric assay is described for the determination of plasma nifedipine using nitrendipine as an internal standard. Chromatographic separation was performed on a dimethylsilicone capillary column, and detection was by selected ion monitoring of electron impact-generated base peak ions. The lower limit of quantifiable detection of nifedipine was 2 ng/ml. The method was applied to plasma samples obtained from a human subject who had been dosed with a 10-mg nifedipine capsule every 8 h for eight doses.

Gas Chromatography-Mass Spectrometry↗
PubMed1989

Gas chromatographic-mass spectrometric analysis of plasma oxybutynin using a deuterated internal standard.

A gas chromatographic-mass spectrometric method is described for the quantitative analysis of plasma oxybutynin. Deuterated oxybutynin served as the internal standard and its synthesis is described. Chromatographic separation on a methylsilicone capillary column avoided the thermal decomposition observed using a packed column. Electron-impact ionization and selected-ion monitoring of the alpha-cleavage fragments of drug and internal standard permitted quantitation of oxybutynin down to 0.25 ng/ml of plasma. At the 2 ng/ml level the accuracy and precision are 4 and 10%, respectively, and improved at higher drug concentrations. Application of the method to the pharmacokinetics of oral oxybutynin in man demonstrated rapid absorption and elimination of the drug.

Chemical Phenomena↗
PubMed1988

Circadian rhythm in theophylline disposition during a constant-rate intravenous infusion of aminophylline in the dog.

The disposition of theophylline in three dogs was determined during a 48-h constant-rate intravenous infusion of aminophylline. A systematic fluctuation in serum theophylline concentrations was observed over a 24-h period, which appeared to be characteristic of a circadian rhythm. Neither assay variability nor fluctuations in the infusion pump rate could account for the observed variations in the serum concentrations. It was concluded that the changes in the theophylline concentrations were the result of a circadian rhythm in theophylline disposition.

Aminophylline↗
PubMed1988

Effect of pH on the in vitro dissolution and in vivo absorption of controlled-release theophylline in dogs.

Dogs were used to examine the effect of elevated gastric pH on the absorption of controlled-released theophylline dosage forms with pH-dependent dissolution. In vitro studies showed that a controlled-release theophylline tablet dissolved more rapidly if it was initially exposed to an acidic media. In contrast, a controlled-release theophylline beaded capsule was slightly more rapidly dissolved in the absence of an initial exposure to an acidic media. Gastric pH was increased from 0.5-2.5 to 4.5-7.0 in four dogs by using 150-mg ranitidine HCl tablets, administered every 3 h, to induce an achlorhydric condition. Gastric pH was monitored using a Heidelberg capsule. Ranitidine was shown to have no apparent effect on the absorption or clearance of theophylline administered to the dogs as an oral liquid. The mean area under the concentration-time curve to infinity (AUCinf) for the controlled-release theophylline tablet was 21% greater (p less than 0.05) when administered to the four dogs without ranitidine treatment, compared with that following dosing with ranitidine. In contrast, the controlled-release beaded capsule exhibited a 10% greater AUCinf when ranitidine was given concomitantly. In general, ranitidine-induced changes in the in vivo absorption rate parameters for both dosage forms were opposite to those predicted from the in vitro dissolution rates. The results of this study demonstrated that the extent of theophylline absorption from controlled-release dosage forms, in control dogs and dogs with ranitidine-induced achlorhydria, corresponds to the pH-dependent in vitro dissolution properties of the products.

Animals↗
PubMed1986

Dialyzability and pharmacokinetics of indomethacin in adult patients with end-stage renal disease.

Indomethacin, a nonsteroidal antiinflammatory drug, has been shown to be effective for the treatment of pericarditis in chronic hemodialysis patients. Data regarding the dialyzability of indomethacin in these patients, however, is lacking. The aim of this study, therefore, was to evaluate (1) the dialyzability, and (2) the absorption and elimination kinetics of indomethacin, using six stable anephric adult patients who were maintained on chronic hemodialysis and were receiving indomethacin for the management of their uremic pericarditis. The results from this study demonstrate that indomethacin is dialyzable, but not to an appreciable extent. The mean predialysis and postdialysis indomethacin plasma levels were 3.4 and 1.6 micrograms/ml, respectively. The mean total amount of indomethacin removed by five hours of hemodialysis was 19.6 percent of the single dose of indomethacin 100 mg po. However, mean Cpmax, tmax, t1/2, and AUC0-infinity during and in the absence of hemodialysis were 5.4 and 5.4 micrograms/ml (not statistically significant [NS]), 1.9 and 2.0 h (NS), 6.1 and 5.3 h (NS), and 30.9 and 35.7 micrograms h ml-1 (NS), respectively. Based on these findings, it can be concluded that although indomethacin is dialyzable, no dosage adjustment is required in patients receiving indomethacin for the management of their uremic pericarditis when undergoing maintenance hemodialysis.

Adult↗
PubMed1985

Bioavailability of dyphylline and dyphylline-guaifenesin tablets in humans.

A six-way-crossover bioavailability study was conducted with twelve healthy male volunteers to evaluate the relative bioavailability of three tablet formulations containing dyphylline and three tablet formulations containing dyphylline-guaifenesin. Each subject was administered two tablets of each product with greater than or equal to 3 d separating each dose. Blood samples were obtained just prior to each dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, and 10.0 h following each dose. An HPLC method was used to assay dyphylline in the serum. The mean tmax ranged from 0.6 to 1.0 h for the six products. The mean values for Cmax differed by 29%, and the AUC values differed by less than 8%. It was noted that the dyphylline-guaifenesin products exhibited a lower bioavailability than the products which only contained dyphylline. It was concluded that the three combination products were bioequivalent, as were the three dyphylline products.

Adult↗
PubMed1985

Determination of free disopyramide plasma concentrations using ultrafiltration and enzyme multiplied immunoassay.

Disopyramide is an antiarrhythmic drug that exhibits nonlinear binding to plasma proteins. As a result, the total body clearance increases with increasing total drug plasma concentration. A rapid and sensitive method for the determination of free (unbound) disopyramide plasma concentrations is described. The procedure employs an ultrafiltration system (Centrifree), which can be used for basic drugs, along with an enzyme multiplied immunoassay system (EMIT) for the measurement of free disopyramide concentrations in plasma water filtrate. The EMIT method was adapted to permit measurement of disopyramide in plasma over a concentration range of 0.02-1.2 micrograms/ml. Plasma storage at -20 degrees C, filtration volume, or the presence of buffer and mono-N-dealkylated metabolite in plasma did not affect the binding determinations. There was no loss of drug during the filtration process. A good correspondence was found between the EMIT assay and a high performance liquid chromatography method, when applied to plasma samples obtained from a human subject who had ingested disopyramide. Furthermore, the extent of protein binding determined by the ultrafiltration system and by equilibrium dialysis were in good agreement. The binding of disopyramide in fortified human plasma decreased from 64 to 52% over a total drug concentration range of 1-5 micrograms/ml.

Blood Proteins↗
PubMed1984

Absorption of phenobarbital from tablets and elixir.

A three-way crossover study was conducted with 24 healthy male volunteers to determine the relative bioavailability of four different 100-mg phenobarbital tablets compared with a reference elixir. Each subject received two of the tablets and the elixir at 30-d intervals. Blood samples were collected daily for 19 d after each dose. Plasma phenobarbital concentrations achieved with the five dosage forms differed by less than 20% within 2-3 h after dosing. The extent of absorption for all dosage forms, as determined from area under the plasma concentration-time profiles, were within 10% of each other. The peak plasma concentration was the greatest and the time to peak concentration was the shortest for the elixir. One of the tablets exhibited a time to peak concentration of 8.6 h, which was significantly longer than any of the other dosage forms. The time to peak concentration correlated with the percent of drug dissolved in 60 min, as determined in 0.1 M HCl, using the USP XX paddle method at 50 rpm.

Adult↗
PubMed1984

Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration.

Healthy male volunteers (N = 24) participated in a four-way crossover study to compare the rate and extent of absorption of naltrexone after administration of 50 mg tablets as 50, 100, and 200 mg doses and a 10 mg/ml reference syrup. A high-performance liquid chromatographic method was employed to measure naltrexone and 6-beta-naltrexol in plasma and urine. Compared to the syrup, the 50 mg tablets were absorbed more slowly but equally well. There was excellent linearity between the administered dose and the area under the plasma concentration-time profile, as well as total urinary recovery of both drug and metabolite. The mean half-lives for naltrexone and beta-naltrexol were approximately 4 and 12 hours, respectively. The fraction of drug reaching the systemic circulation was estimated to be 5% of the administered dose because of extensive first-pass metabolism. Less than 1% of the dose was excreted in the urine as naltrexone after 48 hours, while 25% was recovered as unconjugated beta-naltrexol. The renal clearance of naltrexone and beta-naltrexol was approximately 127 ml/min and 283 ml/min, respectively. The total systemic clearance for naltrexone was approximately 94 L/hr.

Administration, Oral↗
PubMed1983

Phenytoin I: in vitro-in vivo correlation for 100-mg phenytoin sodium capsules.

Dissolution profiles for 11 brands of phenytoin sodium capsules were carried out by the basket and paddle methods (USP) and the spin-filter method. The results from the dissolution studies have been correlated with observed differences in in vivo parameters (Cmax and tmax). The dissolution by the basket method at 50 rpm in water gave a correlation greater than 0.9. The results suggest the existence of two types of phenytoin sodium products on the market.

Biological Availability↗
PubMed1983

In vivo-in vitro correlations with a commercial dissolution simulator II: papaverine, phenytoin, and sulfisoxazole.

The dissolution profiles of 11 commercially available papaverine, phenytoin, and sulfisoxazole dosage forms were determined using a dissolution simulator. The products had been the subject of earlier in vivo bioavailability studies with human subjects. The use of an absorption simulator, which is designed to provide an estimate of the optimum sampling scheme for the dissolution simulator, did not provide useful data for this purpose. Good in vivo-in vitro correlations were found for the papaverine dosage forms, which included nine controlled-release products. Less satisfactory correlations were obtained for the phenytoin capsules and the sulfisoxazole tablet products.

Absorption↗
PubMed1983

Bioavailability of propylthiouracil in humans.

Single lots of five commercially available 50-mg propyl-thiouracil formulations were evaluated in vitro and in vivo. Each product met the USP XIX specifications for drug content, content uniformity, and disintegration time. However, major differences were noted among products in their rate and extent of dissolution. Statistically significant differences (p less than 0.05) were observed in vivo among the drug formulations at all but one of the sampling times, as determined from crossover blood level studies in 12 healthy male volunteers. The differences among the areas under the plasma level-time curves for the various products were not statistically significant. No statistically significant correlations were found between the in vitro and in vivo parameters studied.

Biological Availability↗
PubMed1983

Nonlinear ethotoin kinetics.

Five healthy subjects were given single 500-, 1500-, and 2500-mg doses of ethotoin as 250-mg tablets at 7-day intervals. Plasma samples were collected for 49 hr after dosing and were assayed by HPLC for ethotoin. The drug was more slowly absorbed after the two higher doses. There was a disproportionate increase in AUC in all subjects with the escalating doses. Individual subject data were fitted to a first-order model and one incorporating Michaelis-Menten elimination kinetics. Eleven of the 15 data sets were best described by the nonlinear model. All subjects reported visual disturbances with the two higher doses, and four of five experienced dyscoordination of gait with the 2500-mg dose. These effects did not appear to be related to plasma ethotoin concentration.

Adult↗
PubMed1983

Detection of oxacillin-resistant staphylococci by the AutoMicrobic system.

The AutoMicrobic system (Vitek Systems, Inc., Hazelwood, Mo.) is an automated instrument designed for rapid microbiological identification and susceptibility reporting in the clinical laboratory. The reliability of a rapid, automated approach to testing methicillin-resistant staphylococci was evaluated. To determine the accuracy in detecting oxacillin-methicillin resistance by the AutoMicrobic system, 746 staphylococci from seven different geographical areas were tested. Results were compared with the Bauer-Kirby agar disk diffusion technique as the reference method. Of the 304 staphylococci, 209 coagulase-positive and 95 coagulase-negative strains were resistant to oxacillin-methicillin. These organisms fell into three categories of resistance detection. The first category had resistance levels high enough for initial detection, the second category had low resistance levels requiring modified data analysis techniques for detection, and the third category had resistance levels too low for detection. Of the resistant strains tested, 21% showed a category two resistant growth pattern. Major errors, as a result of hetero-resistant growth patterns of the tested strains, were resolved by computer analysis of growth curves. These data analysis applications enabled detection of 96% of the oxacillin-methicillin-resistant organisms. Results for all resistant staphylococci tested were available in an average time of 5.5 h.

Autoanalysis↗
PubMed1983

Placental transfer of chloroquine in pregnant rabbits.

The pharmacokinetics of chloroquine was determined in pregnant and nonpregnant rabbits following intravenous administration. Blood concentrations of chloroquine and desethylchloroquine in the mother and fetuses were assayed using HPLC. Chloroquine rapidly crossed the placenta, resulting in equivalent fetal and maternal blood concentrations 15-30 min after dosing the mother. The subsequent 1 and 2 hr fetal blood concentrations were about two-fold higher than the corresponding maternal blood concentrations. The desethylchloroquine metabolite blood concentrations were low relative to the drug, although the metabolite was detected in all blood samples including the initial 5 min maternal blood samples and 15 min fetal blood samples. Comparing the pharmacokinetics of chloroquine in the pregnant and nonpregnant animals revealed no difference in total body clearance. However, there was an approximately two-fold decrease in the apparent volumes of distribution and terminal half life in the pregnant rabbits. Because of the relatively large inter-animal variability in these parameters, the differences were not statistically significant (p greater than 0.05), but do indicate a trend toward changes in chloroquine pharmacokinetics during pregnancy.

Animals↗
PubMed1981

Urinary excretion of methenamine and formaldehyde: evaluation of 10 methenamine products in humans.

The urinary excretion of both methenamine and formaldehyde was measured for 48 hr after the oral administration of 10 different methenamine products to 10 human subjects in a crossover study. The following dosage forms were evaluated: a tablet of methenamine base, a methenamine hippurate tablet, and eight products containing methenamine mandelate, including six enteric-coated tablets, a suspension, and a granule dosage form. The nonenteric-coated dosage forms were absorbed more rapidly, based on maximum excretion rates that occurred within 3 hr after dosing. The enteric-coated tablets, which were designed not to release methenamine until reaching the intestinal tract, exhibited maximum excretion rates that did not occur until 7-17 hr after dosing. There were no significant differences (p greater than 0.05) among products in terms of total excretion of free formaldehyde in the urine. However, large differences (p less than 0.05) were noted among products for urinary recovery of total methenamine, with the amount of administered dose recovered ranging from 16 to 83%.

Adult↗
PubMed1981

In vivo-in vitro correlations with a commercial dissolution simulator. I: Methenamine, nitrofurantoin, and chlorothiazide.

Dissolution profiles were determined for nine methenamine, 14 nitrofurantoin, and six chlorothiazide dosage forms using a dissolution simulator. Various in vivo-in vitro correlations were examined. The best correlation for methenamine was between the maximum urinary excretion rate and the time for 15% dissolution. A good correlation for the 50-mg nitrofurantoin tablets was also found between cumulative percent of drug excreted in 12 hr and the percent dissolved in 1 hr. There were no significant correlations for the 100-mg nitrofurantoin dosage forms. Good correlations were also observed for the 250- and 500-mg chlorothiazide tablets between the percent of drug dissolved in 1 min or the time for 15% dissolution and the maximum excretion rate.

Absorption↗