G. Segre

Relation between morphine pharmacokinetics and analgesia

The relationship between the multicompartmental behavior of morphine and the kinetics of the analgesic effect has been investigated using a digital computer compartment analysis program. The results obtained indicate that the concentrations of morphine in the brain are not related to the analgesic effect in a “direct” manner but rather in an “indirect” way. A compartment model describing the kinetics of such an “indirect” pharmacological effect was found to yield a good correlation between the Pharmacokinetics of morphine and the kinetics of the analgesic effect.

Plasma acth and cortisol levels in benzodiazepine treated rats

Summary In rat a single i.p. administration of various benzodiazepines (bromazepam, chlordiazepoxide, clonazepam, diazepam, flunitrazepam, flurazepam, medazepam, nitrazepam) at doses equivalent to those employed in humans brings about a clear-cut decrease of ACTH levels in plasma, without changes in plasma cortisol levels. The repeated administration (0.5 mg/kg every 24 hours for 4 days) of diazepam, in addition to a decrease of plasma ACTH levels, brings about a decrease in plasma cortisol levels.

Multicompartmental analysis of serum, urine and bile concentrations of rifampicin and desacetyl-rifampioin in subjects treated for one week

Summary o 1) A multicompartmental analysis of the serum, urine and bile concentrations of rifampicin and of its desacetyl-derivat i ve was carried out in man in order to assess the simultan e ous distribution of the two compounds during repeated trea t ment. 2) The results have shown that the desacetyl-derivative repr e sents only a small fraction of the antibiotic present in serum and that this fraction decreases with time. This finding suggests that the decrease in biological half-life observed in the early phase of continuous treatment with rifampicin involves the antibiotic in its unchanged form. 3) The decrease in the serum rifampicin levels was accompanied by an increased biliary excretion which involves mainly the metabolic derivative. 4) The kinetic analysis appeared to indicate that the rate of intestinal absorption of the antibiotic increases with time as does the rate of biotrasformation of rifampicin into d e sacetyl-rifampicin.

The lymphatic route—II. Pharmacokinetics of human recombinant interferon-α2 injected with albumin as a retarder in rabbits

The aim of the present investigation was to define whether multisite subcutaneous (s.c.) administration in unanesthetized, unrestrained rabbits of human recombinant interferon-alpha 2 (rec. IFN-alpha 2) either in saline, human albumin (ALB) solution (4, 7 and 10% final concentrations), or in a solution containing 75 U of hyaluronidase, modified the pharmacokinetic parameters calculated from the IFN plasma levels. Plasma disappearance rates of rec. IFN-alpha 2 were measured in rabbits after intravenous (i.v.) administration and the kinetic was adequately represented by a three-pools mammillary model. This model was the basis for evaluating the absorption and distribution of rec. IFN-alpha 2 after s.c. administration. The increase of ALB concentration (from 4 to 10%) caused a significant reduction of the plasma IFN Cmax while both the mean residence time and the release time of IFN increased linearly with the ALB concentration. The data support the postulation that s.c. administration of albumin acts as an interstitial fluid expander and may favour absorption of IFN via lymphatics rather than blood capillaries. Improvement of therapeutic index of IFN by using this route remains to be shown in clinical trials.

The kinetics of ouabain uptake in frog heart in relation to the kinetics of inotropic effect and to the activation of transport ATP-ases

Summary In frog heart in vivo and in vitro the kinetics of the inotropic response to ouabain and the kinetics of the heart uptake of the drug were studied. The time course of ouabain uptake in various heart subcellular fractions and the activation of transport ATP-ases have been determined. The calculated amount of ouabain taken up by frog heart and by microsomal and sarcoplasmatic fractions is in keeping with the activation of transport ATP-ases.

Compartmental analysis of the effect of carbon tetrachloride intoxication on blood and bile kinetics of sulfobromophthalein in rats

In rats intoxicated by CCl4 (2.5 ml/kg by stomach tube or 10 ml/kg i.m.), the plasma and bile BSP kinetics were fitted to a four-compartment model. The effect of CCl4 was analyzed by the changes brought about in the five transfer constants which characterize the model. Intrahepatic BSP transfer and liver uptake are the parameters most sensitive to CCl4 intoxication. The peak effect is obtained 1 day after the intoxication, with a rapid return to normality.

The sojourn time and its prospective use in pharmacology

AbstractSojourn time in a given compartment i when the material has been injected in compartment j (Sji) corresponds to the average time spent by the particles of the material in i before their definitive exit from that compartment. Sojourn time is different from the mean residence time

Pharmacokinetics of rufloxacin in healthy volunteers

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