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The objective of this work was to develop a population physiologically based pharmacokinetic (popPBPK) model to characterize the variability in the clinical PK of monoclonal antibodies (mAbs) following intravenous (IV) and subcutaneous (SC) administration. An extensive literature search was conducted and clinical PK data for FDA-approved as well as non-approved mAbs were collected. Training and validation datasets of 44 and 9 mAbs exhibiting linear pharmacokinetics were used for model development. The variability in antibody PK was captured by accounting for different rate constants of pinocytosis (CL up ) and intracellular degradation (k deg ) for different mAbs. Typical values for CL up and k deg and their respective inter-antibody variabilities (ωClup, ωKdeg) were estimated to be 0.32 L/h/L and 26.1 h-1 (73% and 46%). Varied absorption profiles following SC dosing were characterized by incorporating inter-antibody variability in local degradation (k SC ) and rate of lymphatic uptake (S_Lu) of mAbs. Estimates for typical k SC and S_Lu values, and ωKsc,ωS_Lu, were found to be 0.0015 h-1 and 0.54 (193%, and 49%). FDA-approved mAbs showed less local degradation (0.0014 h-1 vs. 0.0038 h-1) compared with other clinically tested mAbs, whereas no substantial differences in physiological processes involved in disposition were observed. To evaluate the generalizability of estimated PK parameters and model validation, the final popPBPK model was used to simulate the range of expected PK for mAbs following SC administration of nine different mAbs that were not used for model-building purposes. The predicted PK of all nine mAbs was within the expected range specified a priori . Thus, the popPBPK model presented here may serve as a tool to predict the clinical PK of mAbs with linear disposition before administering them to humans. The model may also support preclinical-to-clinical translation and 'first-in-human' dose determination for mAbs.

The authors report 9 cases of rhinosporidiosis observed in Côte d'Ivoire. Young subjects are generally concerned with E.N.T. and eye manifestations. There is a male preponderance. Pathological aspects are classical. Surgery has been the only treatment with good results.

In 1988 to 1989, 698 adult cadavers in Abidjan's two largest morgues were studied, representing 38 to 43% of all adult deaths in the city over the study period, and 6 to 7% of annual deaths. Forty-one percent of male and 32% of female cadavers were infected with human immunodeficiency virus (HIV). Fifteen percent of adult male and 13% of adult female annual deaths are due to acquired immunodeficiency syndrome (AIDS). In Abidjan, AIDS is the leading cause of death and years of potential life lost in adult men, followed by unintentional injuries and tuberculosis. In women, AIDS is the second leading cause of death and premature mortality, after deaths related to pregnancy and abortion. AIDS-specific and AIDS-proportional mortality rates may be higher in other African cities where AIDS has been found for a longer time than in Abidjan.

The authors described a case of generalised and lethal Pentastomiasis by a five years old girl. The most heavy parasitised organs are the lungs and the brain. Considering the age of the child and the uncommon density of the parasites, the authors suggest that the symptoms may follow the casual ingestion of a gravid female worm.

Constrictive endocardial fibrosis (CEF) or endomyocardial fibrosis (EMF) was studied on 14 files of this rather frequent disease in Ivory Coast. On the basis of the data derived from angiocardiography, catheterization and mechanograms, the clinical signs are interpreted better. Thus one is able to describe with accuracy some clinical forms, the commonest of which being a right heart restriction combined with left-sided signs. It seems important underline how useful the external pulse recordings might be useful for the diagnosis in view of their analogy with the pressure curves. In this disease with a severe course, bold surgical treatments provide some hope. On the contrary, its aetiology remains mysterious. Our best landmark being the link of CEP with tropical ecology, and in particular, in our cases, with the warm and damp forest ecology of some areas.

The authors study the epidemiological conditions of the appearance of Burkitt's disease on the Ivory Coast. This condition represents 4.12% of cancers observed in this country. From a thorough study of the differences in temperature, relative humidity, vapour pressure, hours of sunlight, amount of rainfall, they were able to pick out that equatorial forest zones are more at risk than the savannah zones. The climatic conditions in the forest render intervention by a vector plausible, either directly or indirectly via malaria or other parasitic infestations.

Our conception of Bilharziosis, one of the oldest known illness, has been considerably modified during the last twenty years with the development of Immunology. In fact, it is now established that the severity of the illness depends upon the importance of granuloma which arises round the emprisoned egg in the tissues and the sclerosis mutilation which follows. It is possible to describe, successively around the egg, exsudative granuloma, productive granuloma, and sclerocicatricial nodule whose size will depend upon the tissular immunity. In particular this granuloma will be practically non-existent when the endogenic desensitization of the subject is maximal. In this case the egg will remain undestroyed and there will be egg's calcification in the tissue. Contrarily, in the case of minor tissular immunity there will be serious collagenous mutilations as in Symmers hepatic fibrosis. It is therefore preferable that a histopathological study be part of the routine investigations of this disease: it confirms itself as one of the best prognostic criteria.