Bioavailability of amoxicillin and clavulanic acid from extended release tablets depends on intragastric tablet deposition and gastric emptying.

The rate and extent of amoxicillin and clavulanic acid absorption from pharmacokinetically enhanced extended release (ER) tablets is strongly influenced by the intake conditions. In order to investigate the cause of the food effects, a pharmacokinetic study with simultaneous imaging of the in vivo behaviour of the ER tablets by magnetic marker monitoring (MMM) was performed. Under fasting conditions the amoxicillin AUC (1854+/-280microg min ml(-1)) was significantly lower than after intake at the beginning of the breakfast (2452+/-354microg min ml(-1)) or after the breakfast (2605+/-446microg min ml(-1)). In contrast, clavulanic acid AUC was well comparable after tablet intake under fasting conditions and intake at the beginning of a breakfast (191+/-46 and 189+/-44microg min ml(-1), respectively) but significantly lower following a breakfast (126+/-71microg min ml(-1)). The localization data showed that the reduced bioavailability of amoxicillin under fasting conditions is due to early gastric emptying in combination with poor absorption from deeper parts of the small intestine. Prolonged gastric residence of clavulanic acid caused by intragastric tablet deposition in the proximal stomach was identified as the reason for the decreased bioavailability of clavulanic acid after tablet intake following the meal.

Tissue oxygen pressure (ptO2) in extracellular volume expansion and hypervolemic polyglobulia.

Muscle tissue oxygen pressure (ptO2) was measured in rats employing the microwire platin electrode according to Kessler and Lübbers. In extracellular volume expansion up to 50% above the normal volume the ptO2 histograms are situated within the normal range. Increase of the interstitial space for oxygen diffusion seems to be effectively counterbalanced by increased cardiac output. In hypervolemic polyglobulia, hematocrit about 60%, four rats presented normal ptO2 levels. In one animal only the ptO2 histogram was shifted to the left (lower values); in this rat also cardiac output was considerably reduced.

Cardiovascular system and tissue oxygen pressure (ptO2) in bilaterally nephrectomized rats.

1. In bilaterally nephrectomized rats, 24 or 44 +/- 2 h after surgery, normal distribution of tissue pO2 values was measured at the surface of liver and thigh muscles. 2. As cardiac output was generally higher in uremic rats as compared with that of corresponding controls and arterial pO2 was rather elevated in the uremic rats, it may be concluded that the cells of the uremic animals were sufficiently supplied with oxygen. 3. Consequently, the known depression of whole body oxygen consumption in acute uremic rats must be due to metabolic defects at the cellular level. 4. Elevated arterial blood pressure in acute uremic rats is due to elevated cardiac output which in turn is mainly caused by fluid retention. When uremic rats are deprived of water the increase of blood pressure, cardiac output and plasma volume are considerably blunted.