Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients.
Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.5 +/- 14.6 mg of Hx-Ara were removed by one PE during the first week of treatment (15 mg kg-1 d-1, continuous infusion) and 7.8 +/- 10.2 mg were eliminated by one PE during the second week of treatment (7.5 mg kg-1 d-1, continuous infusion). Based on the vidarabine intake per hour and the resulting quantity of Hx-Ara removed per hour, PE recovery was quite important (ca. 30 per cent), during both the first and second weeks of continuous infusion. Data were subject to large interindividual variability. However, these results do not favor vidarabine dosage supplementation in this indication because the duration of PE is less than 8 per cent of a daily administration period. For paracetamol (1 g, single oral dose) and diclofenac (100 mg, single oral dose), the fractions of drug removed during PE effected within 2 h of drug intake, were respectively 5.0 +/- 3.1 per cent and 13.6 +/- 9.5 per cent, while plasmapheretic clearance reached, respectively, 13.0 +/- 10.7 per cent of the systemic clearance for paracetamol and 23.0 +/- 1.0 per cent for diclofenac.
Département de Pharmacologie-Hospitalière, Hôpital Avicenne, Bobigny, France.
F
F
Fauvelle
P
P
Nicolas
A
A
Leon
M
M
Tod
G
G
Perret
O
O
Petitjean
L
L
Guillevin
D000082:Acetaminophen / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D004008:Diclofenac / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D010488:Polyarteritis Nodosa / Q000378:metabolism*; D014740:Vidarabine / Q000493:pharmacokinetics*
D004008:Diclofenac; D000082:Acetaminophen; D014740:Vidarabine