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Studies on the toxicology of hexachlorobenzene. I. Pharmacokinetics.

In female rats dosed orally with 14C-hexachlorobenzene the extent of intestinal absorption of carbon-14 has been found to be dependent on the form of application. When the substance was given as a solution in oil about 80% of the dose administered was absorbed, but when given as an aqueous suspension only 6%. In animals treated with 14C-hexachlorobenzene dissolved in oil, all tissues contained radioactivity. Highest levels were found in adipose tissue, lowest in blood and muscle. Peak values of radioactivity were reached between 2 to 5 days after application. Elimination was studied after intraperitoneal application of 4 mg/kg14C-hexachlorobenzene dissolved in oil. Two weeks after administration, 34% of the radioactivity administered was recovered in the feces and 5% in urine. About 80% of carbon-14 excreted in feces and about 4% in urine was contained in the unchanged drug. This indicates that biodegradation of hexachlorobenzene in the rat is not insignificant. No radioactivity was detected in the expired air.

Adipose Tissue↗

The effect of renal failure on the disposition and neuromuscular blocking action of pancuronium bromide.

Plasma concentrations of pancuronium following single dose administration in six patients, and following multiple dose administration in four patients, all undergoing renal transplantation surgery, were measured using a fluorimetric method. A two-compartment open model was used in the pharmacokinetic analysis of the data. Comparison of the pharmacokinetic findings with data previously obtained for patients undergoing elective surgery but having normal renal function indicated that the clearance of the drug was reduced significantly in the patients with renal failure, and that in these individuals the half-life was increased significantly. Measurement of the evoked mechanical twitch response concurrently with plasma concentration monitoring of pancuronium confirmed that the prolongation of half-life in the patients with renal failure was often but not always associated with an extended duration of neuromuscular blockade and furthermore that the rate of recovery from block might also be prolonged. The clinical implications of these findings are discussed.

Adult↗

Literature growth in pharmacokinetics.

The literature growth in pharmacokinetics and bioavailability between the years 1964 and 1980 is analyzed. During much of this period, the literature doubled approximately every 1.6 years. However, during the period 1978-1980, little or no growth was observed. During the period 1950-1967, the total chemical literature increased exponentially with a half-life of 8.28 years; between 1968 and 1980, the half-life was 12.4 years. Thus, the pharmacokinetic literature increased at a much more rapid pace than did the total chemical literature in general. The subject of growth is considered in a general context, particularly as influenced by psychological, sociological, political, and economic factors. It is concluded that while mathematical functions may adequately describe past literature trends, they have little if any utility in predicting future trends in specific research areas such as pharmacokinetics.

Abstracting and Indexing↗