Biomedical subjects

A M Mattocks

Publications and source records attributed to A M Mattocks.

7 recordsLinked to original sources

PubMed1979

Nonlinear model for acetazolamide.

Intravenous bolus injections of 14C-labeled acetazolamide were made in rabbits. Plasma, urine, and washed red blood cell concentrations were measured, the latter indicating bound drug. AUTOAN and NONLIN were used to fit the plasma data to a linear two-compartment model. However, utilization of the urine and red blood cell data suggested that a nonlinear model was more appropriate. The developed nonlinear system uses a one-compartment model with two tissue-binding parameters. The system simultaneously fits three equations describing drug in the plasma, in the body, and bound to red blood cells, Six parameters were estimated. The initial plasma concentration and the maximum amount bound to tissue protein (minus red blood cell protein) correlated with dose. The dissociation constant from this protein fraction suggested that it is composed mainly of the enzyme, carbonic anhydrase. The dissociation constant for the red blood cell fraction suggested that the drug binds to other protein in addition to carbonic anhydrase. The elimination constants were quite similar, indicating little variation from one animal to another. Utilization of the concepts of site and mechanism of action in this model should be of considerable help in relating drug concentration to pharmacological resonse.

Acetazolamide↗

PubMed1979

Relationship of pharmacokinetics to pharmacological response for acetazolamide.

Acetazolamide concentration values derived from a nonlinear model system were related to two pharmacological responses in the rabbit. Kidney response was measured by monitoring urine flow and sodium elimination. Ocular response was followed using an applanation tonometer. Maximum urine flow and sodium elimination occurring immediately after injection correlated with log dose. Urine flow dropped below control values along with a rise in osmolality, suggesting the involvement of antidiuretic hormone. Sodium elimination was correlated with plasma levels. Urine pH is thought to be involved in reducing accessibility of drug to carbonic anhydrase in the kidney. Maximum ocular response also was correlated with log dose. Ocular response was related to a protein fraction, which is believed to be mainly carbonic anhydrase. However, the duration of ocular response was related to the red blood cell protein fraction. Thus, drug activity could conceivably be regulated by monitoring a tissue that is not the site of action and can be sampled readily.

Acetazolamide↗

PubMed1979

Creatinine kinetics in the rabbit.

To evaluate the kinetics of creatinine in the rabbit, two radiotagged creatinine forms were used, with 14C in the amidino group or with it in the carboxyl group. Five animals were injected intravenously with tracer amounts, and plasma samples were taken for 250-300 min; urine and feces samples were taken over longer periods. A chromatographic method was used to separate unchanged creatinine from other components of the samples prior to measurement for chemical and radioactivity content. Equations for the proposed flow model were derived and fitted to specific activity data, and values for transfer constants, production rates, and pool sizes were calculated. Evidence supported the concept that a two-compartment model is required and that production occurs in the peripheral compartment. Evidence also indicated that muscle represented a major part of the peripheral compartment. Small amounts of metabolites, chiefly guanido compounds, were detected when amidino-labeled creatinine was used. Also, small amounts of unchanged creatinine and metabilites were found in the feces.

Animals↗

PubMed1978

Quantitative TLC determination of propranolol in human plasma.

A spectrodensitometric assay was developed for propranolol based on measurement of the absorbance of the drug on silica gel plates irradiated at 822 nm. Quantities as low as 0.10 microgram can be detected, and a linear relationship was obtained between 0.010 and 0.400 microgram. The percent recovery from plasma spiked with known amounts of the drug was 90.0--102.0. This procedure was used to determine propranolol in the plasma of patients receiving therapeutic doses of the drug.

Chromatography, Thin Layer↗

PubMed1977

Specific thin-layer chromatographic method for the determination of quinidine in biological fluids.

A sensitive, accurate and specific spectrodensitometric method has been developed for the determination of quinidine in biological fluids. It involves extraction of quinidine, dihydroquinidine and metabolites, their separation on thin layers and quantitation of the corresponding spots by direct scanning in a densitometer at 278 nm. A linear relationship was obtained between the ratio of the peak area of an unknown sample to that of the standard and the concentration of the compounds at 0.4-4microgram/ml. The recovery from plasma was from 96 to 103% for quinidine and from 93.5 to 98.5% for dihydroquinidine. A comparison was made between this thin-layer chromatographic method and the fluoriemtric assay frequently used for the determination of quinidine in plasma at present. The method is recommended for clinical assays and pharmacokinetics studies.

Animals↗

PubMed1977

Quantitative thin-layer chromatographic method for the determination of procainamide and its major metabolite in plasma.

A sensitive and accurate spectrodensitometric method was developed for the determination of procainamide and its major metabolite, N-acetylprocainamide, in plasma. The method involves extraction into organic solvent at alkine pH, separation by thin-layer chromatography and direct measurement of the absorbance of the compounds on the plate at 275 nm. Quantities as low as 10 ng could be measured and a linear relationship was obtained between peak areas and amounts of the compounds in the spots from 10 to 200 ng. The recovery of both drugs from plasma was from 95.4 to 104.8%. The method is sensitive and specific, and procainamide was well separated from N-acetylprocainamide at all investigated concentrations. The method is recommended for clinical assays and pharmacokinetics studies.

Chromatography, Gas↗

PubMed1975

Specific thin-layer chromatographic method for the determination of theophylline in plasma in the presence of some other drugs.

A simple spectrodensitometric method for the direct determination of theophylline was developed from measurement of the absorbance of the compound on silica gel layers irradiated at 275 nm. Auantities as low as 0.010 mug can be detected and a linear relationship was obtained between peak area and the amount of the drug in the spots from 0.025-0.200 mug. The recovery over the usual range of plasma concentration (2.5-20 mug/ml) was 95-107%. The method is sufficiently sensitive and specific for clinical purposes and the time for the assay is about 2 h. Caffeine, frequently present in human plasma, was well separated from theophylline at all concentration levels as were several other drugs commonly used in respiratory problems.

Absorption↗