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Biomedical subjects

M W Anderson

Publications and source records attributed to M W Anderson.

186 records · Page 11Linked to original sources
PubMedDate not supplied

Effect of chlorination on the distribution and excretion of polychlorinated biphenyls.

The distribution and excretion of four 14C-labeled polychlorinated biphenyls (PCB), 4-chloro-, 4,4'-dichloro-, 2,4,5,2',5'-pentachloro-, and 2,4,5,2',4',5'-hexachlorobiphenyl, were studied in the rat. Total radioactivity was determined in the major organs and tissues at times varying from 15 min up to 42 days after an intravenous injection of a single 0.6-mg dose of each of the PCB's per kg. Each of the PCB's was removed rapidly from the blood and initially stored largely in the liver and muscle. The rates of the subsequent redistribution of the PCB's and their metabolites to the adipose tissue and skin and/or excretion could be related to the degree of chlorination. The relative amounts of each PCB and its metabolites in each major tissue were determined at selected time points. The percentage of the total radioactivity accounted for by metabolites of the PCB's decreased as the chlorination of the PCB's increased, but storage of metabolites did not account for a significant portion of any of the PCB doses. Excretion accounted for more than 90% of the dose of the mono-, di-, and pentachlorobiphenyls during the time period studies, whereas extrapolation of the hexachlorobiphenyl data indicated that less than 20% of the dose would ever be excreted. The rates of elimination of the PCB's were apparently determined primarily by their rates of metabolism. The effect of degree and position of chlorination on the rate of metabolism of the biphenyl molecule is discussed.

Adipose Tissue↗
PubMedDate not supplied

A study of the dynamics of imipramine accumulation in the isolated perfused rabbit lung.

An isolated perfused rabbit lung preparation (IPL) was used to study the uptake, accumulation, and efflux of the tricyclic amine imipramine (IMIP). The rate of IMIP uptake into the IPL was resolved into two exponential components (rates 1 and 2 of uptake). The initial velocities for these uptake components were linearly related to the concentration of IMIP in the perfusate (Cp). This linear relationship indicates that IMIP accumulated in the IPL by diffusion and/or binding. The steady-state accumulation of IMIP was obtained by integration of the exponential expression relating the rate of IMIP uptake to time. The amount of IMIP accumulated at steady state by rate 1 was linearly related to Cp, whereas the amount of IMIP accumulated at steady state by rate 2 was saturable with respect to Cp. These steady-state data are in agreement with the steady-state accumulation data previously reported from experiments with the recirculating blood-perfused rabbit lung. In the absence of IMIP in the perfusate. IMIP that had previously accumulated in the IPL effluxed from the lung at three rates (t1/2 = 18 sec, 58 sec, and 8.25 min), which indicates that accumulated IMIP was in at least three pools in the lung. In addition, a noneffluxable pool was detected which was not the result of irreversible binding to tissue.ated in pools 1 and 2 by rate 1 of uptake. The IMIP in pool 3 and in the noneffluxable pool was accumulated in the IPL by rate 2 of uptake. Efflux pool 3 and the IMIP accumulated at a steady state by rate 2 of uptake were resolved by a Hofstee plot into a biphasic curve indicating two types of binding sites. The noneffluxable pool of IMIP in the IPL was saturable with increasing Cp and represented approximately 30% of the IMIP accumulated by rate 2 into pool 3. Rate 2 of uptake, pool 3, and particularly the noneffluxable pool of IMIP in the IPL are possibly responsible for the accumulation and persistence of Imip in the lung as seen in whole body distribution studies. The physicochemical properties of IMIP and other compounds known to be accumulated in lung tissue are discussed in relation to the possible involvement of lung phospholipids and the compartmentalization of IMIP in the concentric lamellar organelles of the lung.

Animals↗
PubMedDate not supplied

Studies on the persistence of basic amines in the rabbit lung.

We have investigated the time-course of the pulmonary deposition of imipramine (IMIP) following a single iv injection into rabbits. A pool of IMIP and its demethylated metabolites, which exhibited considerable persistence (half-life of decay = 4 hr), was formed in the lung. This pool, now called the slowly effluxable pool (SEP), appears to be synonymous with the noneffluxable pool (NEP), which we have previously shown to be formed with IMIP in the isolated perfused lung (PL). Furthermore, this pool appears to be responsible for the pulmonary persistence of IMIP, inasmuch as 24 hr after an iv injection it contributes greater than 90% of the total lung concentration. Chlorphentermine and methadone formed SEP's in the IPL of comparable size to that formed with IMIP, whereas phentermine formed a considerably smaller SEP. These results suggest that the degree of hydrophobicity of the amine is an important determinant of the size of the SEP formed. This further supported by the lack of an SEP with the relatively polar amines, 5-hydroxytryptamine and amphetamine. The 10-fold difference in the size of the SEP for compounds known to induce pulmonary phospholipidosis (chlorphentermine and IMIP) and known not to induce lipidosis (phentermine and amphetamine) may suggest a possible involvement of the SEP in the onset of phospholipidosis; this possibility is discussed.

Amines↗
PubMedDate not supplied

Comparison of the pharmacokinetics of several polychlorinated biphenyls in mouse, rat, dog, and monkey by means of a physiological pharmacokinetic model.

Physiologic pharmacokinetic analysis of 4,4'-dichlorobiphenyl, 2,2',3,3',6,6'-hexachlorobiphenyl, and 2,2',4,4',5,5'-hexachlorobiphenyl is presented for the dog and monkey, and the results are compared with previous similar analyses for the rat and mouse. The normalized clearances (ml/min/kg body weight) vary considerably between the dog and the monkey; the rat and the mouse show less species variation. The equilibrium tissue-to-blood distribution ratios for parent and metabolite are generally similar for all four species. The fat compartment has the highest parent distribution ratio for all four species, and the metabolite distribution ratios are much smaller than the parent distribution ratios. Metabolism appears to be a prerequisite to urinary and biliary excretion for all three compounds in each species. Elimination from the body occurs predominantly by the fecal route. The 2,2',4,4',5,5'-hexachlorobiphenyl is more slowly metabolized than the 2,2',3,3',6,6'-isomer in all species, which supports the contention that two adjacent, unsubstituted carbon atoms on the biphenyl ring promote more rapid metabolism.

Animals↗