Activated charcoal impairs propantheline absorption

Summary 5 g activated charcoal BPC reduced the effects of 45–60 mg of propantheline given orally at the same time. This interaction may be important in patients taking remedies containing charcoal. Patients suffering from overdosage with quaternary ammonium compounds administered orally might benefit from immediate treatment with activated charcoal.     

Absorption kinetics of a series of local anesthetics from rat subcutaneous tissue. I

The subcutaneous absorption kinetics of a homologous series of local anesthetics and lidocaine were studied under controlled pH conditions using a previously described in vivorat model. All local anesthetics exhibited biexponential absorption profiles suggesting accumulation into a tissue compartment. Evidence supporting this hypothesis was supplied by back-extraction of lidocaine from subcutaneous tissue into an acidic environment, by multiple dosing experiments, and by movement of compound into subcutaneous tissue of a postmortem rat preparation. A series of interanimal relationships were demonstrated between structure and parameters of a twocompartment open model. Particularly striking were the correlations between in vivopartition and tissue clearance and the octanolwater (pH 7.95)partition coefficients.Supported by National Institutes of Health Training Grant No. 5T01 GM 00728 from the National Institute of General Medical Sciences and by research funds from the Academic Senate Committee on Research, University of California at San Francisco.Abstracted in part from a thesis submitted by René H. Levy to the Graduate Division, University of California at San Francisco, in partial fulfillment of the Doctor of Philosophy degree requirements.This paper was submitted to a Consulting Editor who served as the Journal Editor during its review process.     

Effect of route of administration on drug disposition

While the first-pass effect is a fairly generally understood phenomenon in the gross sense, it is not commonly appreciated that the rate at which the drug is delivered to the liver can influence the fraction of the administered dose which reaches the fluids of distribution. The drug molecules being absorbed via the hepatic portal vein intermix with previously absorbed drug recycling in the hepatic artery. The concentration of the drug returning via the hepatic artery is affected by the volume of distribution of the drug into body tissues (and the relative partition of the drug between the blood and the tissues). If one presumes that liver uptake is controlled by a Michaelis-Menten process of metabolism, it can be readily shown that the extent of extraction of the drug by the liver is controlled not only by the Michaelis-Menten constants, but also by the concentration of the drug transitting the liver per unit time. The effects of dose, rate of absorption, partitioning, and tissue distribution characteristics are systematically discussed and referred to in relation to selected examples of drugs in common use.The work reported here was supported in part by grant NIGMS16496-05.Presented by S. Reigelman at the Conference on Pharmacology and Pharmacokinetics: Problems and Perspectives, October 30–November 1, 1972, at the Fogarty International Center, National Institutes of Health, Bethesda, Maryland. This paper, in a slightly different format, will be published in the Proceedings of the Conference by Plenum Press, New York.     

Effects of different rates of absorption of two benzodiazepins on subjective and objective parameters

Summary Two benzodiazepins with different rates of absorption have been compared in a double-blind cross over study in six healthy subjects using single doses of diazepam (Valium) 2, 5 and 10 mg and oxazepam (Sobril) 15, 25 and 50 mg. Further, oxazepam formulations with different rates of absorption have been compared in 8 healthy subjects. Lastly, the diurnal variation in serum levels during long-term therapy with the benzodiazepins has been followed up in a pilot study in hospital. Drug influence was assessed at intervals and showed that the quantitative and qualitative subjective effects as well as the alteration of reaction time and hand steadiness were more pronounced during the rising phase than in the constant plateau or falling phase of serum drug concentrations. Rapidity of increase in concentration appeared more important than the absolute level. Diazepam has the faster rate of absorption and had a significantly (p<0.05–0.001) greater influence at 30 min, and usually at 90 min, too, than oxazepam or the placebo. Oxazepam, even when administered as a formulation with near-maximal absorption rate, still had not high enough a rate of absorption to produce the distinctly identifiable onset of reactions characteristic of diazepam and did not give noticeable prolongation of reaction time or increased hand unsteadiness even at its maximal serum concentrations. The separate pilot study showed that relatively large diurnal variations in serum concentrations might occur during continuous treatment for more than four weeks and that a preparation with a high rate of absorption (diazepam) could still produce a subjectively apparent experience after each individual dose. It seems reasonable to assume that the risk of abuse, and equally also one of the factors increasing the risk of habituation to psycho-pharmaceutical drugs, is related to subjectively experienced effects, which, as shown above, depend to a large extent on the rate of absorption. For maintenance treatment a steady serum level adapted to the individual is probably to be preferred, while in acute treatment, for example, of attacks of anxiety, a compound with rapid absorption is required, and the therapeutic advantages must then be weighed against the greater risk of abuse.     

Arsenic determination in autopsy material using atomic absorption spectroscopy

Summary In a case of fatal arsenic intoxication samples of blood, liver and bile were analysed using atomic absorption spectroscopy. Different flames were used. The liver sample was ashed in a low temperature asher. The method is simple and requires a minimum of sample handling.The authors are thankful to Asbjørn Granseth for technical assistance in this work.     

Effect of colestipol,a new bile acid sequestrant,on the absorption of phenprocoumon in man

Summary The effect of colestipol, a basic anion-exchange resin, which lowers the serum cholesterol level, has been examined on the absorption of phenprocoumon in four human volunteers,in vivo. Plasma concentrations of phenprocoumon were determined after the simultaneous ingestion either of 8 g colestipol or 4 g placebo (microcrystalline cellulose) and 12 mg phenprocoumon according to a randomized crossover repetition design. The plasma levels were not affected by colestipol, suggesting that it had no effect on the absorption of phenprocoumon. —In vitro, the phenprocoumon-binding capacity of colestipol was the same as that of cholestyramine, except in buffers at pH 5 when there was a marked decrease in the colestipol binding.     

RECENT CLINICAL CORRELATES OF VITAMIN D METABOLITES AND CALCIUM METABOLISM

Several types of bone disease are related to abnormalities in the metabolism of vitamin D. The synthetic 1-OH hydroxycholecalciferol appears to have considerable potential as a therapeutic agent.     

Delayed absorption of lithium in intoxication

Summary A 55-year old man with lithium intoxication showed increasing serum concentrations in spite of forced diuresis and dialysis. A high lithium content was found in gastric juice three days after the compound had been taken. The serum lithium level began to fall after gastric lavage.