PHARMACOKINETIC CHANGES IN PATIENTS WITH EDEMA

The pharmacokinetics of furosemide (frusemide)in patients with oedema have been relatively well studied, but in many studies it is unclear w hether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decrease d, but total bioavailability was almost unchanged, The peak serum conc entration (C-max) and time taken to achieve C-max were either decrease d or unchanged. Binding of furosemide to plasma proteins is lower in p atients with congestive heart failure (CHF), decompensated liver cirrh osis (DLC) and nephrotic syndrome, probably as a result of hypoalbumin aemia. The elimination half-life (t(1/2))can be unchanged (CHF, DLC) o r prolonged (chronic renal failure: CRF). Plasma and renal clearance a re reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly respon sible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clin ically relevant. The pharmacokinetics of digoxin have been studied in: a small number-of studies only. In patients with CHE considerable inte rindividual differences have been found, Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oed ematous patients. Theophylline has higher bioavailability in patients with edema, with a significantly higher C-max in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectivel y). Furthermore, clearance decreases and t(1/2) increasesinthese patie nts. Angiotensin converting enzyme (ACE) inhibitors are often administ ered as prodrugs, and their pharmacokinetic profile could be influence d by the diseases that accompany oedematous states. However, the effec t of oedema is difficult to discriminate from that of the disease. Ind ividual ACE inhibitors are affected differently, but importantly the d osage of perindopril should be reduced in patients with CHE while for most other ACE inhibitors the changes in pharmacokinetic parameters ar e clinically irrelevant. In conclusion, studies on pharmacokinetic cha nges in oedema are limited. Besides affecting absorption (after oral a dministration) acid conversion of the prodrug to the active form, prob ably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameter s for individual drugs. However, further studies of this aspect of pha rmacokinetics are needed.