Penetration of aztreonam into pleural exudate following rapid intravenous bolus or constant infusion.

A study on the effects of the mode of administration on aztreonam (AZ) concentrations in pleural fluid was performed in human subjects. The same dose of AZ was given as an intravenous bolus injection to one group and as a drip infusion to another group of patients. Serum and pleural fluid samples were collected at different times after drug administration, and the antibiotic concentrations were measured by using a microbiological method. The highest serum and pleural exudate concentrations and area under the curve values were obtained after drip infusion. These results indicate that drip infusion gives higher concentrations of AZ in pleural effusion.

Effect of age on single- and multiple-dose pharmacokinetics of erythromycin.

The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d. for 7 doses. The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses. Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively). The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h). No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution. The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults. Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance. The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people.

Pharmacokinetics of miocamycin in patients with liver cirrhosis.

The pharmacokinetics of miocamycin, a new macrolide antibiotic, was studied in 6 healthy controls and 6 patients with compensated liver cirrhosis. The results indicate that in chronic liver disease the kinetics of the drug is altered. Therefore, a dosage adjustment of miocamycin is recommended when dealing with these patients.