Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer.

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h⁻¹ (range 176-726 l h⁻¹). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P=0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P=0.04) and ABCC1 g.7356253C>G (P=0.04).

Flowers and other trigger factors in asthma and rhinitis--an inquiry study.

Six hundred and eighty adult patients with asthma and/or rhinitis were questioned about symptoms elicited by 46 different flowers and 10 common non-specific environmental trigger factors listed in a questionnaire. Flowers or birch twigs were reported to elicit symptoms in 79% of the patients, somewhat more often in rhinitis than in asthma patients, and caused symptoms as often in non-atopics as in atopics. Birch twig and marguerite most frequently induced symptoms, followed by strongly smelling flowers such as hyacinth, lilac, and lily of the valley. Unspecific irritants caused symptoms in 98% of the asthmatics and in 67% of patients with rhinitis. Tobacco smoke and perfumes were the most important troublemakers. A significant positive correlation was found for elicitation of symptoms from flowers and from certain non-specific irritants. It is concluded that non-specific hyperreactivity as well as reaginic hypersensitivity are the mechanisms involved when birch twigs and flowers elicit symptoms.

Hyposensitization in hay fever with grass pollen extracts: a three-year study comparing a dialysed alum adsorbed extract with allpyral.

Immunotherapy with a dialysed aqueous extracted alum absorbed extract of grass pollens and with undialysed pyridine extracted alum precipitated extract of grass pollens (Allpyral) was compared in 58 patients with hay fever over a three year period in a randomized open study. Both types of treatment resulted in similar immunological responses as measured by changes in grass specific serum IgE and IgG. The dialysis of the grass pollen material did not decrease or increase the stimulation of specific immunoglobulins. The incidence of both local and systemic side effects was similar in both treatments. More injection site granulomata occurred in patients treated with the new alum adsorbed extract, although the difference did not achieve statistical significance. Symptom-medication data showed that patients who received the conventional pyridine extracted materials obtained a better clinical response, but all treatments gave continuing clinical benefit in each successive year.

Double-blind comparison between beclomethasone dipropionate as aerosol and as powder in patients with nasal polyposis.

Beclomethasone dipropionate as a pressurized aerosol is effective in nasal polyposis, but the efficacy is only moderate. In these partly-blocked noses, it seems possible that the insufflated drug in powder form is better distributed over the mucous membrane than the pressurized aerosol. To test this hypothesis, we treated forty-two patients with nasal polyposis with intranasal beclomethasone dipropionate as a powder and as a pressurized aerosol in a double-dummy, cross-over design. There was no difference between the treatments in sixteen patients, while in twelve cases there was a preference for beclomethasone dipropionate as aerosol, and in fourteen, for the powder form. Fourteen found the aerosol most irritating and nineteen, the powder. Thus, in a group of polyp patients there were no significant differences between the two application forms, but possibly there is a need for both aerosol and powder, as there appeared to be differences in the individual responsiveness to the two types of intranasal medication. Blind microscopy of wiped nasal-smears before and after beclomethasone dipropionate treatment showed a reduction of basophilic cells, and counting of sneezes after medication demonstrated a reduction in the number of sneezes. These results suggest that a reduction of epithelial mediator-cells and of irritant receptor-sensitivity are of importance for the efficacy of topical steroids in rhinitis.

Topical corticosteroids and nasal reactivity.

The etiology of perennial non-allergic rhinitis and nasal polyposis is still not properly understood. Non-specific hyperreactivity forms a major significant symptom. Topical steroids have been used in the treatment of these diseases for about ten years. Their mode of action is still largely unknown. Various test methods in clinical trials can improve our knowledge. The effect of budesonide given intranasally as an aerosol was tested in 22 patients with perennial rhinitis. In another trial the effect of beclomethasone dipropionate (BDP) was compared when given as an aerosol and as a powder. Today we know not only that budesonide and the two forms of BDP are clinically efficacious but also that intranasal steroid treatment can reduce metacholine-induced nasal secretion, reduce the sensitivity of mucosal irritant receptors, and lower the number of basophilic as well as eosinophilic cells in the nasal secretion.