Biomedical subjects

A Deslandes

Publications and source records attributed to A Deslandes.

4 recordsLinked to original sources

PubMed1992

Adaptive computer program for determination of absorption profiles by numerical deconvolution: application to amoxicillin absorption.

We have developed a specific numerical deconvolution program for the Apple Macintosh microcomputer. After comparison with other methods, we used the program to evaluate the influence of nifedipine on the absorption and bioavailability of amoxicillin. The technique provided a model-independent approach. This study shows that the simultaneous administration of nifedipine with amoxicillin leads to a significant increase in both the total quantity of amoxicillin absorbed (+22%) and the rate of absorption. Parameters of clearance, volume of distribution, and elimination were unaffected. Numerical deconvolution analysis showed that nifedipine did not modify the absorption kinetics of amoxicillin, which are characterized by a lag time followed by a constant rate of absorption, suggesting zero-order kinetics with first-order kinetics at the end of the process. The results suggest the existence of a specialized, saturable transport molecule for this antibiotic.

Adult↗

PubMed1992

Modification of cefixime bioavailability by nifedipine in humans: involvement of the dipeptide carrier system.

We studied the action of nifedipine on the bioavailability of cefixime, a molecule absorbed via the gut wall dipeptide carrier system in the rat, and on the bioavailability of D-xylose, which is absorbed via a pH (and Na(+)-)-dependent transporter. Each compound was administered alone or in combination with 20 mg of nifedipine to eight healthy male volunteers. Nifedipine significantly increased the absorption rate of cefixime (20.7 +/- 4.3 versus 16 +/- 3.5 mg/h in the absence of nifedipine). The absolute bioavailability of cefixime alone was 31% +/- 6% compared with 53% +/- 1% (P < 0.01) in the presence of nifedipine. The observed peak concentrations in serum were significantly different (2.5 +/- 0.3 mg/liter without nifedipine and 3.7 +/- 1.1 mg/liter with nifedipine; P < 0.02). In contrast, nifedipine induced no significant differences in the pharmacokinetic profile of xylose following oral administration. We conclude that (i) cefixime is absorbed in humans by an apparently active process which can be enhanced by a calcium channel blocker, in this case, nifedipine; and (ii) nifedipine does not modify the activity of the pentose transporter.

Administration, Oral↗

PubMed1991

Reappraisal of amoxycillin absorption kinetics.

Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process. Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine. In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers. The results showed evidence of a saturable carrier-mediated uptake of this antibiotic. With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism.

Administration, Oral↗

PubMed1990

Nifedipine enhances amoxicillin absorption kinetics and bioavailability in humans.

Intestinal absorption of aminopenicillins in vitro uses the dipeptide carrier system. Recent experiments have reported calcium ion to be a cellular mediator of the regulation of electrolyte transport through the enterocyte membrane, especially the Na/H exchange which is partly responsible for the proton gradient energizing the carrier system. In order to assess the in vivo relevance of these data, we studied, in healthy volunteers, the influence of nifedipine, a calcium channel blocking agent, on the intestinal uptake of amoxicillin, a commonly prescribed and well-absorbed aminopenicillin. Results obtained show that 1) intestinal absorption kinetics of amoxicillin follows a zero-order process, which further substantiates the existence of a saturable carrier-mediated process for this antibiotic in humans and 2) calcium channel blockade significantly enhances both absorption rate (by 70%) and bioavailability of amoxicillin (by 21.4%) without modifying its distribution or elimination. These findings might suggest that nifedipine could enhance amoxicillin intestinal uptake by stimulating its active transport.

Adult↗