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Five white rabbits are given by rectal route a single dose of 100 mg of Aspirin at regular hours: 7 a.m.; 10 a.m. and 2 p.m. the 7 a.m. administration results in lowest CMAX and AUC and the slowest elimination, whereas 10 a.m. and 2 p.m. administration results in the highest CMAX and AUC and shortest elimination time.

The results of a survey conducted in a company employing 1850 persons working in air-conditioned premises are reported. One hundred and five persons were examined, including 790 who mostly complained of respiratory disorders and 20 controls. Regular check-ups during the last two years have failed to reveal any serious disease. The most frequent complaints were rhinitis and tracheitis, especially among female employees. No alveolitis was observed. The finding of Bacillus subtilis in samples of ambient air and air-conditioner filters in conjunction with the presence of precipitating antibodies against crude extracts from these samples, suggested that the respiratory disorders might have been due to this microorganism. A multifactorial analysis demonstrated a statistically significant correlation between clinical symptoms and immunological disorders. The air-conditioner disease, therefore, may present as a benign condition.

In this study we demonstrate that the dissolution rate and gastroduodeno-cecal transit time of radiolabeled tablets of theophylline can be determined in vivo using technetium-99m (99mTc). Six healthy male volunteers ingested a tablet containing 300 mg of theophylline mixed with 3.7 MBq of [99mTc]DTPA. Anterior and posterior scintigraphic views of the abdomen were collected serially over 8 hr, after which a 200-ml solution containing 37 MBq of [99mTc] pertechnetate was ingested in order to visualize the contours of the stomach. The in vivo activity contained in the tablet was calculated from the scintigraphic views after correction of background activity, radioactive decay, and depth attenuation. The dissolution rate of [99mTc] DTPA was also measured in vitro and compared with the dissolution rate of theophylline. The results showed close dissolution rates between [99mTc]DTPA and theophylline in vivo (T1/2 184 min and 176 min, respectively), and a faster early dissolution rate of [99mTc]DTPA in vitro (T1/2 92 min versus 156 min for theophylline). The mean gastroduodenal and duodenocecal times were 72 +/- 25 min (m +/- s.d.) and 245 +/- 15 min, respectively. Scintigraphic imaging of labeled formulations with 99mTc present useful applications in pharmaceutics and pharmacology.

The aim of this study is to compare the bioavailability of acetylsalicylic acid administered rectally in suppositories form and orally in tablets form to the rabbit. Acetylsalicylic acid was given to 8 males rabbits rectally and orally in a balanced crossover design with 15 days of interval between each study. In blood samples, acetylsalicylic acid is determined by Trinder's method. It has been established that the rectal route has a faster absorption than the oral route however it displayed a more intense first pass effect than that of the oral route.

A double blind study of thiophene carboxylate in 32 chronic bronchitis patients, show an improvement of clinical and respiratory condition in the treated group. However, there is no increase in volume of expectoration and no fluidizing. The product acts as mucoregulator, the reorganization of fibrillary mucus allowing a better efficiency of mucociliary apparatus.

The authors report 2 cases of hypersensitivity pneumopathy associated with haematological abnormalities: benign lymphoproliferative syndrome in one case, and malignant lymphadenopathy with fatal outcome in the other case. Such cases, now observed with increasing frequency, can be regarded either as chance associations of 2 types of disease, or as the results of immune disorders with repercussions on the blood.

Bidimensional electrophoresis is of most interest for the diagnosis of extrinsic allergic alveolitis. In fact, this detecting method is more specific than classical immunoelectrophoresis. Thus patients showing with the classical methods precipitation lines with one or several antigens do not present everytime the corresponding clinical signs. These positive but false reactions cannot in any case appear with bidimensionnal electrophoresis. Generally, the patient showing at least two precipitation lines opposite one antigen in bidimensional electrophoresis always followed by an increase of IgG, does also present the clinical signs of the disease.

In this work, we have studied in the rabbit, bioavailability of acetylsalicylic acid contained respectively in three forms of suppositories which are made as follows: for the first by only acetylsalicyclic acid (0.1 g); for the second by the association: acetylsalicylic acid (0.1 g) and phenobarbital (0.01 g); and for the third by acetylsalicylic acid (0.01 g), ascorbic acid (0.02 g) and thiamine chloride (0.002 g). It has been shown that ascorbic acid and thiamine chloride do not change the bioavailability of acetylsalicylic acid, while phenobarbital decreases it. In this work we have also compared two pharmaceutical forms of suppositories containing acetylsalicylic acid, ascorbic acid and thiamine chloride. In one of the two forms, acetylsalicylic acid is buffered by glycocolle. The study which consisted in giving the two forms to the rabbit rectally was concerned with the effect of glycocolle on the bioavailability of acetylsalicylic acid. It was shown that making glycocolle a buffer to acetylsalicylic acid resulted in an improved absorption as well as a delayed elimination of acetylsalicyclic acid. In this study too, we have evaluated the bioavailability of acetylsalicylic acid which is released from two types of suppositories containing respectively base witepsol W31 and base cocoa butter. In order to study this bioavailability whole suppositories were administered by rectal route to the rabbits after 24 hours of fasting (balanced crossover design with 15 days of interval after each study). Statistical analysis does not reveal any significant difference between the two forms of suppositories.

In order to evaluate the influence of food and time of administration on the absorption of diethylamine chromocarbe, a bioavailability study was performed in 8 volunteers by using a new method of plasmatic drug evaluation. The results obtained indicate that lunch has little effect on diethylamine chromocarbe absorption in comparison with the administration 0.5 h before breakfast. The bioavailability parameters Cmax, tmax, and AUC are not statistically different and the two methods of administration can be considered as bioequivalent. The absorption of diethylamine chromocarbe seems to be reduced when the drug is administered before dinner. This delay on absorption may be due to circadian rhythm of tractus gastrointestinal absorption or to the reduction of physiological activity of volunteers.

Precipitins against avian antigens in sera from patients with extrinsic allergic alveolitis, asymptomatic pigeon and chicken breeders and from control individuals were tested with different antigen extracts in six laboratories by a variety of different methods. Eighty percent of the results coincided in identifying the positive sera from patients and 90% in identifying the controls. It seems possible therefore to exchange results among experienced laboratories with fair confidence.

The in vitro and in vivo dissolution of a sustained release theophylline formulation labeled with 99mTc-diethyltriaminepentaacetic acid (DTPA) has been monitored in six subjects with a scintillation camera. The study was performed in fasting conditions and was repeated after ingestion of a standardized meal. Results showed that the presence of food in the stomach dramatically increased the oesoduodenal transit time of the tablet (74 +/- 27 min vs 352 +/- 77 min, P less than 0.001) but did not modify the biodisponibility of theophylline. This study is another example when scintigraphy can be of definite value in pharmacokinetics.

The aim of the study was to investigate the pharmacokinetic modelling of Cefotaxime (CTX) and its main metabolite Desacetyl Cefotaxime (DCTX) which has a less antibacterial activity than the CTX. After intravenous administration of lg of CTX to 26 patients, the plasma concentrations determined by HPLC showed that the pharmacokinetics of CTX and transformation to DCTX can be described with an open five-compartment model. The implications of this are discussed from the clinical point of view.

Two series of work are reported. The first concerns the pharmacocinetic study of the product after it was administered through different ways and the corresponding evolution of PaCO2. The second study concerns the effect on pulmonary arterial pressure, blood gases and some parameters of ventilatory mechanics, of a perfusion of 200 mg of this product over a two hours period.

Tobacco may act as an allergenic or immunogenic agent, the antigen being present in either leaves or smoke. It is capable of producing immediate hypersensitivity reactions with respiratory disorders or cardiovascular lesions through a mechanism involving interaction between basophils and IgE. It may also induce the production of IgG-type antibodies, the significance of which remains to be elucidated. Finally, tobacco interferes with cell-mediated (alveolar macrophages, lymphocytes) lung defense mechanisms in normal subjects or patients. Any interpretation of some pathological conditions associated with tobacco should take these immunological reactions into account.

Microcomputers have been used in pharmacokinetics for several years, but their use in the area of formulation is a new application. By using appropriate data on the drug, the dosage form required and its mechanism of absorption and clearance, microcomputers can systematize and speed-up formulation, simplify manufacturing processes and, through simulated models and plasma level predictions, reduce the number of bioavailability studies needed.