Joseph Costermans

Effect of Hemodialysis On Plasma Kinetics of Fenofibrate in Chronic-renal-failure

The influence of hemodialysis on plasma fenofibric acid kinetics has been investigated in patients with chronic renal failure given 300 mg of fenofibrate in a single oral dose. A very pronounced lengthening of the fenofibric acid plasma decay was observed in both hemodialyzed (n = 6) and nonhemodialyzed (n = 9) patients. Hemodialysis did not modify the plasma levels and the ultrafiltrates contained very small amounts of fenofibric acid. The repeated daily administration of 100 mg of fenofibrate during 2 weeks in 5 renal patients on regular hemodialysis resulted in increasing plasma levels and led to progressive cumulation of fenofibric acid. Plasma fenofibric acid conjugates could not be detected. No particular clinical side effects or increase of CPK, GOT, GPT were be observed.

Oral Bioavailability of Ampicillin and Amoxycillin Alone and Bound in Fixed Proportions to Sulbactam and Clavulanic Acid

Oral bioavailability of ampicillin when bound to sulbactam (sultamicillin) compared with ampicillin alone and that of amoxycillin with a ligand of clavulanic acid versus amoxycillin alone were assessed in 16 healthy subjects using an open label, multiple crossover study. After a single administration of the drugs, the bioavailability of ampicillin released from sultamicillin was more than twice (2.17) that of ampicillin administered alone, whereas that of amoxycillin was increased by a factor of 1.64 by the presence of clavulanic acid. Higher peak concentrations and areas under the curves, along with shorter lag times, were observed in both cases. The increased oral bioavailability of these aminopenicillins when associated with a β-lactamase inhibitor was well demonstrated in this study, the bioavailability of ampicillin being more enhanced by sulbactam than that of amoxycillin by clavulanic acid.

The Metabolic-fate of C-14 Or S-35 Labeled Tiadenol in Rabbit After Iv and Oral-administration

SummaryTiadenol is a hypocholesterolemic drug that inhibits the early steps of cholesterol synthesis. No pharmacokinetic data have thus far been reported for man and few for animals.We investigated the pharmacokinetics, biotransformation and distribution of two differently labelled tiadenol molecules (1 4C and35S) in the rabbit. Following a short protocol (up to 8h), a regular decrease of the plasma radioactivity was observed after i.v. route for 4 or 5h and plateaued therafter. Most of the radioactivity was found in the urine, the lungs and the liver with low levels in bile and feces. By oral route, the plasma radioactivity increased regularly and decayed for a short period. Therafter, a second increase was observed. Drug and metabolites accumulated in the kidneys and in the liver but most of the radioactive compounds were recovered from the urine.From results obtained with a longer protocol (4 days in a metabolic cage), it could be extrapolated that 10 to 15 days are necessary to completely clear the drug. Tiadenol was extensively metabolized with a wide tissue distribution. The main metabolites identified were oxidation products (free or conjugated). No statistically significant differences in biotransformation were found between the two differently labelled tiadenol molecules.

The Time It Takes To Make Judgments of Velocity

Reaction times were measured in an absolute judgment experiment involving either the location of a point on a screen, or the direction of a moving point, or its velocity. Stimuli were chosen to be almost perfectly detectable and discriminable when presented pairwise to avoid confusions at the sensory coding level. Typical results associated with absolute judgment tasks, were observed, as to the amount of information transmission and anchoring effects. More in particular, latencies appear to be a direct function of the number N of alternatives. For N constant, responses are much slower for velocity than for both location and direction. This difference itself is a direct function of N, and, presumably, drops to zero for N = 1, i.e., when stimulus uncertainty vanishes. These observations support the idea that the difference should not be attributed to some velocity-specific integration of space and time but to some performance decision strategies in evaluation of magnitude.