Azithromycin, a macrolide antibiotic with an enhanced antimicrobial spectrum, was found to have a longer half-life than erythromycin, with marked tissue penetration. The pharmacokinetics of azithromycin after oral administration were compared with those of erythromycin in rats (200 mg kg-1) and rabbits (80 mg kg-1). Concentrations of azithromycin in liver, lung, kidney, ileum, and brain were higher than serum concentrations. The slow decline in tissue concentrations was evident from the biphasic elimination profile. Thus, advantageous pharmacokinetic properties and the broader antimicrobial spectrum of azithromycin relative to erythromycin appear to further support its therapeutic potential.
The pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged. Binding of furosemide to plasma proteins is lower in patients with congestive heart failure (CHF), decompensated liver cirrhosis (DLC) and nephrotic syndrome, probably as a result of hypoalbuminaemia. The elimination half-life (t1/2) can be unchanged (CHF, DLC) or prolonged (chronic renal failure: CRF). Plasma and renal clearance are reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly responsible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clinically relevant. The pharmacokinetics of digoxin have been studied in a small number of studies only. In patients with CHF, considerable interindividual differences have been found. Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oedematous patients. Theophylline has higher bioavailability in patients with oedema, with a significantly higher Cmax in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectively). Furthermore, clearance decreases and t1/2 increases in these patients. Angiotensin converting enzyme (ACE) inhibitors are often administered as prodrugs, and their pharmacokinetic profile could be influenced by the diseases that accompany oedematous states. However, the effect of oedema is difficult to discriminate from that of the disease. Individual ACE inhibitors are affected differently, but importantly the dosage of perindopril should be reduced in patients with CHF, while for most other ACE inhibitors the changes in pharmacokinetic parameters are clinically irrelevant. In conclusion, studies on pharmacokinetic changes in oedema are limited. Besides affecting absorption (after oral administration) and conversion of the prodrug to the active form, probably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameters for individual drugs. However, further studies of this aspect of pharmacokinetics are needed.
Diclofenac was isolated from plasma by double extraction with organic solvent. Chromatography was performed on Lichrosorb NH2 column with acetonitrile and perchloric acid (0.0025 mol/l; 35:65, v/v) as the mobile phase (flow rate 0.9 ml/min). The electrochemical detector was operated at +900 mV and sensitivity of 5-10 nA. The sensitivity of the method was 10 μg/1 and the coefficients of variation below 10% in the entire range of the concentration in a dose interval.
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