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Biomedical subjects

M Maccari

Publications and source records attributed to M Maccari.

At least 19 recordsLinked to original sources

Evaluation of pharmacokinetics, bioavailability and dose linearity of diltiazem in healthy volunteers.

The objective of this randomized five-way cross-over study with healthy male volunteers was to determine, one the one hand, the bioavailability and main pharmacokinetic parameters of 4 sustained release diltiazem (Surecaps, CAS 42399-41-7) test preparations with ascending doses (180, 240, 300, 360 mg), administered as single application, versus an immediate release 60 mg diltiazem reference preparation, which was given thrice a day at 8-h intervals. On the other hand, the study also allowed the evaluation of a possible dose linearity of the test substance diltiazem. Plasma concentrations of diltiazem and its major metabolite desacetyl-diltiazem were measured by high pressure liquid chromatography (HPLC) up to 48 h after single dosing of the sustained release preparations as well as after repeated doses of the immediate release formulation. The undesired side effects/concomitant symptoms observed are known to occur after diltiazem administration. For the area under the curve, e.g. calculated from time 0 to the last quantifiable sample (AUC0-Tlast), the study revealed for the parent compound diltiazem mean values of 926.2, 1602.4, 1873.2 and 2415.7 h.ng/ml after administration of the 4 sustained release test preparations, respectively; for the immediate release reference preparation the value was 1007.2 h.ng/ml. Concerning the main metabolite desacetyl-diltiazem the corresponding values for the 4 sustained release formulations were 138.6, 236.9, 280.2 and 345.6 h.ng/ml, respectively. The corresponding value for the immediately release formulation was 127.5 h.ng/ml. Concerning a possible dose linearity of diltiazem, statistical analysis revealed a convincing linear relationship between at least 3 of the 4 sustained release preparations, therefore linearity may be assumed between 240 and 360 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Origin of secretions after denervation of the small intestine in the dog].

The origin of the severe diarrhea appearing after intestinal denervation or transplantation was studied on the 3rd and 14th postoperative days in 5 groups of dogs undergoing total or partial denervation. The net movements of water and electrolytes were investigated by employing an experimental model of intestinal perfusion in isolated loops in vivo. The active uptake of phenylalanine and beta-methylglucoside and Na(+)-K(+)-ATPase activity were used for in-vitro evaluation. Bacteriologic and histological specimens were also taken. Following total denervation with anastomosis, a considerable loss of water and electrolytes as well as numerous E. coli were found in the entire small intestine. This net secretion is due to the stagnation of bacteria in the presence of complete denervation and the absence of food since the animals in this group could not eat properly following general anesthesia and surgery. Consequently, peristalsis was not stimulated and bacterial overgrowth occurred. In the group denervation with pseudo-anastomosis, perfusion studies showed a decrease of absorption in the jejunum and minimal but significant secretion in the ileum. A high number of E. coli was also present. Since the mucosa remained intact, nutrition per os was resumed in the immediate postoperative period and excessive water and electrolyte loss was avoided. The high number of bacteria was due to a decrease in intestinal motility since complete denervation was performed. In the denervation group, water and electrolyte movements were identical to those observed in the preceding group but the entire intestine remained sterile.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bactericidal activity of erythromycin in the respiratory system.

In vivo and in vitro studies were carried out to assess tha levels in bronchial mucus of ampicillin, amoxycillin, bacampicillin, cefotaxime and erythromycin, and to compare their minimum bactericidal concentrations and killing rate against hospital strains of Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae. Both the percentage ratios of serum/mucus concentration peaks and of serum/mucus area under the concentration time curve values were higher for erythromycin than for the other antibiotics. Determination of the minimum bactericidal concentrations showed that the bacterial strains were sensitive to small quantities of erythromycin, and the time necessary to sterilize inocula varied from 4 to 16 hours.

Amoxicillin↗

Stability of frozen rat plasma containing different antibiotics.

The antibiotic activity was determined at different intervals of time on plasma samples, taken from rats treated with a certain number of commonly used antibiotics, and kept at -20 C up to 8 weeks. The results of the microbiological assays demonstrate that the stability of the antibiotics in the frozen plasma decreases in the following order: oxytetracycline > cephalexin, streptomycin, erythromycin > demeclocycline > ampicillin, amoxycillin > penicillin G, cephaloridine, rolitetracycline, and tetracycline.

Animals↗