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G Pifferi

Publications and source records attributed to G Pifferi.

64 records · Page 4Linked to original sources
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Comparative pharmacokinetics of silipide and silymarin in rats.

The plasma level profile and the biliary excretion of silybin, the main flavanolignan component of silymarin, were evaluated in rats after single equimolar oral doses (200 mg/kg, expressed as silybin equivalents) of the silybin-phosphatidylcholine complex silipide (laboratory code IdB 1016) and of silymarin. Silybin was assayed by using a specific HPLC method which allowed also the determination of other flavanolignans present in the biological fluids after administration of silymarin (i.e. silydianin, silycristin and isosilybin). After oral silipide, silybin reached peak plasma levels within 2 h, with a Cmax of 9.0 +/- 3.0 micrograms/ml for unconjugated drug and 93.4 +/- 16.7 micrograms/ml for total (free + unconjugated drug). Maximum total biliary concentrations of silybin (2989 +/- 568 micrograms/ml) were observed within 2 h and the biliary recovery after 24 h accounted for about 13% of the administered amount. After administration of silymarin, unconjugated and total plasma silybin levels as well as biliary excretion were several-fold lower than those observed after treatment with silipide. Silybin recovered over a 24 h period after silymarin intake accounted for about 2% of the administered dose. Plasma and bile obtained after administration of silymarin contained also silydianin, silycristin and, to a greater extent, isosilybin. The concentrations of the latter compound in plasma and in bile were higher than those of silybin itself. The relative bioavailability of silipide (calculated in the target organ as the ratio between AUCs of cumulative biliary excretion curves) was 10-fold higher than that of silymarin.

Animals↗
PubMedDate not supplied

Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects.

IdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin levels were determined after administration of single oral doses of IdB 1016 and silymarin (equivalent to 360 mg silybin) to 9 healthy volunteers. Although absorption was rapid with both preparations, the bioavailability of IdB 1016 was much greater than that of silymarin, as indicated by higher plasma silybin levels at all sampling times after intake of the complex. Regardless of the preparation used, the terminal half-life was relatively short (generally less than 4 h). In a subsequent study, 9 healthy volunteers received IdB 1016 (120 mg b.i.d., expressed as silybin equivalents) for 8 consecutive days. The plasma silybin level profiles and kinetic parameters on day 1 were similar to those determined on day 8. Most of the silybin present in the systemic circulation was in conjugated form. Less than 3% of the administered dose was accounted for by urinary recovery of free plus conjugated silybin, a significant proportion of the dose probably being excreted in the bile. It is concluded that complexation with phosphatidylcholine in IdB 1016 greatly increases the oral bioavailability of silybin, probably by facilitating its passage across the gastrointestinal mucosa.

Administration, Oral↗
PubMedDate not supplied

Comparative pharmacokinetics and bioavailability of two oral formulations of thiocolchicoside, a GABA-mimetic muscle relaxant drug, in normal volunteers.

The comparative pharmacokinetic and bioavailability profile of two different formulations (tablets and capsules) of thiocolchicoside was investigated in 8 healthy male volunteers after administration of single oral 8 mg doses. Plasma samples were assayed by a capillary gas chromatography--mass spectrometry (GC-MS) method following enzymatic hydrolysis of thiocolchicoside to its aglycone (3-demethylthiocolchicine) and no attempt was made to account for the possible occurrence of hydrolysis in vivo. Irrespective of the formulation used, the drug was rapidly absorbed from the gastrointestinal tract, peak levels of about 17 ng/ml being detected within 1 h in most subjects. Elimination was rapid, with mean MRT values of 5-6 h. All kinetic parameters showed considerable interindividual variability but none differed significantly between the two formulations. Relative to the tablet formulation, the oral bioavailability of the capsule formulation was 1.06 +/- 0.39.

Administration, Oral↗
PubMedDate not supplied

The cost benefit ratio of enantiomeric drugs.

Several drugs possess a chiral structure, i.e. they contain one or more stereogenic centres in their molecule. While naturally occurring active principles usually contain a single enantiomer, most chiral drugs produced by chemical synthesis are used in the form of racemic mixtures of two or more diastereoisomers. These stereoisomers (including enantiomers) may interact in different ways with biological structures and, therefore, may exhibit widely different pharmacokinetic properties. In the pharmaceutical industry, partly in response to increasing demands raised by regulatory authorities, these considerations justify the current trend to develop the single enantiomer characterized by the most favourable profile of activity (eutomer). The availability of new chemical and analytical technologies facilitates stereoselective synthetic processes and separation of individual enantiomers from racemic mixtures. Any decision to develop a drug as a single enantiomer, however, should be made only after careful evaluation of the cost-benefit ratio, i.e. when the advantages of the eutomer in terms of efficacy and tolerability outweigh the associated increase in production and development costs with respect to the racemic drug. This article takes into consideration synthetic procedures and pharmacological profiles for a number of chiral drugs in therapeutic use (naproxen, labetalol, and warfarin) or selected for clinical development, such as the beta-blocker dilevalol or the mucokinetic agent 3'-hydroxyfarrerol. These examples demonstrate that the kinetic, pharmacological and toxicological properties of individual enantiomers need to be clearly characterized before any decision can be made concerning the development of a chiral drug. The choice of preferentially developing a single enantiomer should be based on careful consideration of production and development costs and actual therapeutic advantages especially in terms of improved safety.

Animals↗
PubMedDate not supplied

Quality and functionality of excipients.

The quality of medicines depends not only on the active principles and production processes, but also the performance of the excipients. The traditional concept of the excipient as any component other than the active substance has undergone a substantial evolution from an 'inert' and cheap vehicle to an essential constituent of the formulation. The rapid evolution of scientific, regulatory and economic factors, the introduction of delivery systems and the advance in biopharmaceutics have led to a new interest in the role and functionality of the excipients. More than one thousand raw materials are available from a multitude of sources and are used today in the pharmaceutical industry. Their chemical structures vary from small molecules to complex natural or synthetic polymeric mixtures. Excipients are now chosen to perform a variety of functions to guarantee the stability and bioavailability of the drug substance from the drug product and its manufacturability on a production scale. Beyond the dosage form necessities, excipients are required to perform important and specific technological functions, particularly in the case of solid dosage forms. As a consequence, their characterisation must go beyond the simple tests for identity, purity and strength as prescribed in general by the Pharmacopoeia monographs. With the exception of the Textbook of Pharmaceutical Excipients, not many reference sources describing the physical mechanical characteristics of the powders for a specific role are available. Full physical characterisation of solid materials is now made possible with the help of high resolution analytical techniques on the molecular, particulate and bulk levels. This systematic approach is necessary to guarantee the behaviour of the excipient during the formulation and production phases. Some examples have been chosen in this mini-review in an effort to highlight the emerging trends in the development of 'tailor-made' materials. Three main approaches are followed by the industry: physical or minor chemical manipulation of materials already known, combination of two or more marketed excipients in order to reduce unwanted defects and, finally, preparation of new chemical entities with huge investments for the toxicity studies. Excipient harmonisation, standardised functionality tests, preformulation data bases and expert systems will contribute to change the conventional trial-and-error formulation approach into a far more scientific and technological development.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Synthesis of imidazo[2,1-b]thiazoles and thiazolines as potential antiulcer agents.

The replacement of the imidazole ring of cimetidine with a bicyclic system (imidazo[1,2-a]pyridine), reported in the literature, produced compounds endowed with potent antiulcer activity. In this paper we describe the synthesis of imidazo [2,1-b]thiazoles and thiazolines bearing the side chain of metiamide, cimetidine and ranitidine: the compounds obtained, tested on gastric lesions induced in rats by ethanol and by stress, were devoid of antiulcer activity.

Animals↗