Bioavailability of ibuprofen from matrix mini-tablets based on a mixture of starch and microcrystalline wax.

The bioavailability of ibuprofen from matrix mini-tablets based on microcrystalline wax and a starch derivative was tested. An oral dose of 300 mg of ibuprofen was administered to healthy volunteers (n=8) in a randomized cross-over study design either as a commercial matrix formulation (Ibu-Slow 600) or as mini-tablets (filled into hard gelatin capsules). The mini-tablets consisted of 60% ibuprofen, 15% Paracera M (wax), 22.5% DDWM (starch) and 2.5% triacetin (lubricant). t50% of the in vitro release was 4.5 and 5 h for the mini-tablet and Ibu-slow formulations, respectively. Both formulations behaved in vivo as sustained-release formulation; their HVDt50%Cmax value was determined at 5.6 and 5.1 h for the mini-tablet and Ibu-slow formulations, respectively. A significantly higher value of Cmax was seen for the mini-tablet formulation, resulting in a relative bioavailability of 116 +/- 22.6% compared to the Ibu-slow matrix. These data demonstrate that the experimental mini-tablets can be used to formulate sustained-release dosage forms.

A prospective study in healthy volunteers of the topical absorption of a 5% rifaximin cream.

Rifaximin, the active ingredient of an antibiotic cream, is a synthetic antibiotic derived from rifamycin and characterized by minimal absorption. In animals, no absorption was detected after topical application on the skin. The question as to whether there is detectable absorption in man by the same administration route is answered by this study in healthy volunteers. One gram of the cream containing 5% rifaximin was massaged on a sizable surface of skin prepared prior to application by mechanical abrasion. Rifaximin concentrations in blood and urine were then determined by means of HPLC-electrochemical-coulometrical detection. Concentrations in all samples being less than 2.5 ng/ml, the method's limit of detection, it is concluded that there is no detectable absorption in man. No adverse reactions were reported during this one day study. The results confirm studies performed in animals which showed that rifaximin is not absorbed and is well tolerated.

[Diagnosis of allergy in pregnancy]. / Allergiediagnostik in der Schwangerschaft.

Occasionally the allergist is required to examine a pregnant woman because of allergic symptoms. For legal and psychological reasons in particular, and not so much for medical reasons, in vivo allergy tests should be avoided during pregnancy. Consideration of the case history, in vitro tests and avoidance of the possible allergen are recommended for diagnosis at such times. In vivo testing is sometimes necessary if the test results will have substantial implications (for the treatment).

[Contact allergy to a new preservative]. / Kontaktallergie auf einen neuen Konservierungsstoff.

A 43 year old woman with no previous skin disease developed contact eczema on the face and neck after application of a lotion used for "smoothing wrinkels", available as a non-prescription item. Patch testing of the product and of one of its ingredients, Euxyl K 400, revealed strong positive reactions. Upon testing of the individual components of the preservative Euxyl K 400, the substance 1,2-dibromo-2,4-dicyanobutane showed a positive reaction even in the concentration of 0.004%. Due to the increasing use of Euxyl K 400 inclusion of the preservative in the patch test battery should be considered.

[Occupational medicine aspects of cutaneous leishmaniasis]. / Arbeitsmedizinische Aspekte der kutanen Leishmaniose.

Cutaneous Leishmaniasis as an Occupational Disease We report 2 cases of cutaneous leishmaniasis with special regard to its significance for occupational health. Preventive measures are discussed as well as the difficulties in clarifying the diagnosis and therapeutic possibilities.

Replication of HSV-1 in murine peritoneal macrophages: comparison of various virus strains with different properties.

The in vitro replication of eleven different strains of herpes simplex virus type 1 was studied in resident or thioglycollate-stimulated mouse macrophages. The strains of herpes simplex virus differed in the type of cytopathic effect, induction capacity for herpes simplex virus coded thymidine kinase and pathogenicity in the mouse. Herpes simplex virus replicated better in thioglycollate-stimulated macrophages than in resident macrophages. In vitro ageing of macrophages increased their replicative potency. Herpes simplex virus replicated better in macrophages from homozygous bg/bg C57/BL6J mice than in macrophages from their heterozygous littermates. Separation of macrophages on discontinuous Percoll-gradients revealed 4 fractions with identical potency for replication. The ability of herpesvirus to replicate in macrophages varied from strain to strain of virus i.e. Wal greater than Len, clone 4 of Len, greater than L3-2s, JES, Ang-, Ang + path, clone 2 of Len and greater than MDK clones. The ability to cause cytopathology also varied. Only strains Ang- and Ang + path showed limited or late cytopathology in macrophages. The cell-fusing property of herpes simplex virus appeared to be more closely correlated with lower replication rates than production cell rounding. Thymidine kinase- viruses replicated less well than thymidine kinase+ or thymidine kinase(+) strains. Strains of herpes simplex virus with high or low pathogenicity for mice replicated in macrophages to the same degree. The phagocytic activity of macrophages for IgM-coated sheep red blood cells was inhibited earlier by strains of herpes simplex virus of type 2 than by strains of herpes simplex virus of type 1.

Kinetics and genetics of herpes simplex virus-induced antibody formation in mice.

The kinetics of antibody synthesis was investigated after intraperitoneal, subcutaneous, and footpad infection of various strains of mice with herpes simplex virus. Immunoglobulin M antibodies appeared 5 days after and immunoglobulin G antibodies appeared 10 to 12 days after intraperitoneal infection with herpes simplex virus type 1. The major histocompatibility complex and the background genome of inbred mice were not found to have a systematical influence on antibody synthesis. Female mice, however, consistently produced more antibodies than did male if the infection was done intraperitoneally, but not if it was done subcutaneously or into footpads. Castration considerably increased the amount of antibodies produced by male mice. The difference in antibody formation between females and males could be abolished by injection of silica; moreover, antibody titers were enhanced by this treatment. This has also been found by immunization with a Formalin-inactivated herpes simplex virus vaccine. The effect of silica in enhancing antibody formation could be observed up to 12 days after infection. Infectious virus could be detected up to 2 days after infection, and herpes simplex virus type 1 antibody-stimulating antigens could be detected up to 4 days in ultrasonicates of macrophages. The assumption is made that androgen-sensitive cell populations, including macrophages and their soluble products, are involved in antibody-depressing mechanisms.