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G Acocella

Publications and source records attributed to G Acocella.

At least 55 records · Page 3Linked to original sources
PubMedDate not supplied

Pharmacokinetics and metabolism of rifampin in humans.

The unique pharmacokinetic properties of rifampin in humans are discussed in this review. These properties can be better understood by assuming the existence of two pharmacokinetic subsystems; one, the primary subsystem, regulates the time course of the concentration of the antimicrobial agent in the other, the secondary subsystem. The first subsystem includes the intestine and the liver (interconnected through the portal blood and the bile), and the second subsystem includes the tissues, kidneys, and blood of the circulatory system. The connection between the two subsystems in normal conditions is the hepatic veins. The rate of excretion of rifampin in human bile depends, although not exclusively, on its rate of transformation into the biologically active desacetyl derivative. The rate of metabolism increases over the first week(s) of treatment, which results in a corresponding increase of desacetylrifampin excretion in bile. The process is limited and, within a given range of single doses, a transport maximum can be identified. Doses in excess of those associated with the transport maximum generate a more than proportional increase in serum concentrations of the drug. Administration of rifampin causes proliferation of the smooth endoplasmic reticulum of the hepatocyte (probably due to glucuronidation of a fraction of rifampin). This observation explains some of the interactions of rifampin with endogenous and exogenous compounds. The unique distribution of rifampin in human tissues probably results from its capacity to cross biological membranes. Excretion of rifampin in urine does not seem to be associated with any active process.

Animals↗
PubMedDate not supplied

Clinical pharmacokinetics of rifampicin.

After oral administration on an empty stomach, the absorption of rifampicin (rifampin) is rapid and practically complete. With a single 600mg dose, peak serum concentration of the order of 10microgram/ml generally occur 2 hours after administration. The half-life of rifampicin for this dose level is of the order of 2.5 hours. The amount of rifampicin extracted by the liver during its first passage through the hepatoportal system and transferred to bile is relevance for the time course of distribution of the antibiotic in the blood compartment. With dose of the order of 300 to 450mg, the excretory capacity of the liver for the antibiotic is saturated. As a consequence, increasing the dose of antibiotic results in a more than proportional increase in serum concentrations. On repeated administration, and most likely as a consequence of self-induced (autoinduction) metabolism, the rate of disappearance of rifampicin from the blood compartment increases in the early phase of treatment, the phenomenon affecting mainly the levels following the peak, with a consequent reduction in half-life. Approximately 80% of rifampicin is transported in blood bound to plasma proteins, mainly albumin. Rifampicin is well distributed, although to a different degree, in the various tissues of the human body. Probably in the hepatocyte, rifampicin undergoes a process of desacetylation. The metabolic derivative, desacetylrifampicin, is more polar than the parent compound, and microbiologically active. This metabolite accounts for the majority of the antibacterial activity in the bile Rifampicin is almost equally excreted in the bile and urine, the recovery in the 2 fluids being of the same order of magnitude. Administration of rifampicin to newborn infants and children is followed by blood levels generally lower than those found in adults for the same dose levels. In patients with impaired liver and kidney function the elimination of the antibiotic from the blood compartment is slower than in normal subjects. Rifampicin has been found to compete with bilirubin and other cholefil substances for biliary excretion, giving rise to transient and reversible increased bilirubin and BSP retention values. A kinetic model study on the transfer constants between various body compartments has indicated that rifampicin is rapidly absorbed from the intestine and that the absorption rate increases with time. Rifampicin as such is transferred into urine at a rate 3 times higher than the rate of transfer into bile. Desacetylrifampicin, the more polar metabolic derivative of rifampicin, behaves in the opposite way since its rate of transfer into bile is 4 times higher than that into urine. The rate of biotransformation of rifampicin into desacetylrifampicin is of the same order of magnitude as than of biotransformation of the latter into a further metabolic derivative, which could be a glucuronide conjugate...

Anticoagulants↗
PubMedDate not supplied

Eskimo: an epidemiological simulation kinetic model for tuberculosis.

A simple, easy to use, kinetic model allowing the simulation of the main epidemiological parameters of tuberculosis and of the financial costs associated with the implementation of different anti-tuberculous policies, has been developed and described. The model, which has been denominated "ESKIMO" (Epidemiological Simulation Kinetic Model) can be utilized on a personal computer and requires, for its use, the knowledge of a series of easily available census data relative to a given country or geographical area, an essential epidemiological profile of the disease in the same area and data which characterize one or more antituberculous treatments in therapeutic and financial terms. The rationale of the model, which is a multicompartemental system, derive from an analysis of the relationships (transfer rates) between sub-populations of individuals in relation to tuberculosis either when the dynamic state of the system is governed by "natural forces" (no treatment) or when an external action is applied to it with an aim to alter its internal pathways in a favourable sense (vaccination, long-term hospitalization, chemotherapy). The model is based on the assumption that the main objective of any antituberculous program is the reduction in size of the subpopulation of patients who can infect other individuals and therefore perpetuate the disease. Validation and projection tests carried out through Eskimo seem to indicate that concentrating the analysis on the effect of various treatments on this group of patients simplifies the calculations while the relative precision of the estimates of other parameters is very satisfactory. The results of several simulations substantiate and quantify the opinions expressed by several experts in the past that the policy of applying cheap regimens of low efficacy to a relatively small fraction of the patients' population, as frequently done in developing countries, not only does not alter the trend of the disease but produces essentially negative results (increase in the number of new cases and in the frequency of resistant M. tuberculosis). Treatment with highly effective regimens of the same number of patients as those treated now (constant coverage) and therefore without the extra costs resulting from the improvement of the available sanitary infrastructures, produces much better results in clinical terms and overall saving of financial resources.

Computer Simulation↗
PubMedDate not supplied

Past, present and future trends in tuberculosis epidemiology in a region of northern Italy. An analysis carried out through the application of a simulation model (Eskimo).

The epidemiological model Eskimo has been utilized to simulate some epidemiological parameters relative to tuberculosis in a restricted geographical area of northern Italy. After having identified a series of features relative to the regimens applied in the area in the period 1982-86 and which were found to be compatible with the observed data, this hypothesis has been utilized to project data on tuberculosis for the period 1986-1996. The results have indicated that the incidence in the area should stabilize around values of 20 new cases per year (per 100,000 population). A decrease in the incidence can be expected to occur only if the regimens so far employed are brought to a greater part of the patients' population (increasing coverage). The effects of importing the disease from developing countries through immigration and of the AIDS epidemic are likely to negatively affect the trend of tuberculosis incidence in the future.

Cohort Studies↗