Pharmacokinetics of Paracetamol,Diclofenac and Vidarabine during Plasma Exchange

Abstract

In order to establish guidelines for prescribing drugs in patients treated with plasma exchange (PE), we studied the pharmacokinetics of paracetamol (5 patients), diclofenac (4 patients) and vidarabine (3 patients) during one or several PE. Results were compared with those obtained without PE. Diclofenac and paracetamol were choosen because they presented different volume distribution and protein binding characteristics. Vidarabine was studied because we use it for the treatment of patients with polyarteritis nodosa related to hepatitis B virus.

Diclofenac (100 mg) and paracetamol (1000 mg) were given 1 hour before PE. Samples were obtained 60 and 30 min before PE, every 15 min during PE and hourly for 2 hours after the end of PE. Vidarabine was given in continuous infusion, 15 mg/kg/d during the first week of treatment and 7.5 mg/kg/d during subsequent weeks. Samples were obtained before PE, 3 times during PE and every 30 min for 4 hours after the end of PE. Paracetamol, diclofenac, vidarabine and hypoxanthine arabinoside were assayed by high performance liquid chromatography. During each PE 60 ml/kg were removed and replaced by albumin.

We found that 17% of diclofenac, 4.3% of paracetamol and 4.9% of vidarabine were removed during each session. Plasmapheresis clearance was 51% of plasma clearance for diclofenac, 15% for paracetamol and 10% for vidarabine.

Drugs which are mainly removed during PE are those which are bound to proteins with a small distribution volume. Those drugs, such as diclofenac, must be administered after the end of each PE session. Drugs which present a large distribution volume and low protein binding can be given before the session. Vidarabine can be administered during PE without loss of effectiveness due to drug removal.