Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients

Abstract

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.

Pharmacokinetics of ceftriaxone during plasma exchange in polyarteritis nodosa patients

“…The low V and the high degree of protein binding could explain the important effect of PE on the pharmacokinetics of ceftriaxone. The results obtained in a previous study (4) are in complete agreement with this hypothesis. From our results, it follows that the lower the V and the higher the degree of protein binding, i.e., the greater the fraction of the dose administered which is present in the vascular compartment, the greater the elimination by PE and, in turn, the higher the effectiveness of drug removal by PE.…”

“…Twelve polyarteritis nodosa patients undergoing PE were studied. Each patient was given ceftriaxone intravenously in doses of 1 and 3 g on days 4 and 11, respectively, immediately before (n = six patients; group I) and 6 h before (n = six patients; group II) PE. Plasma was assayed for ceftriaxone by high-pressure liquid chromatography.…”

“…However, it must be determined whether the dosage regimen should be modified to replace the drug lost during the exchange procedure. Previous studies (3)(4)(5)10) showed that the volume of distribution (V) and plasma-protein binding are two parameters that may affect the degree of removal of a particular drug by PE, since they provide predictive values for PE effectiveness. This study evaluated the removal of ceftriaxone during PE, and this report describes the relationships between the V and the fraction of the drug eliminated in the removed volume of plasma.…”

Inhibition of Homologous Recombination and Promotion of Mutagenic Repair of DNA Double-Strand Breaks Underpins Arabinoside–Nucleoside Analogue Radiosensitization

“…For araA, concentrations below 100 mmol/L have been reported for patients (47,48), which is at the beginning of the range used in our experiments. For F-araA concentrations between 2 mmol/L and 5 mmol/L (49, 50) have been reported which are much lower than those explored here.…”

Medications in Patients Treated With Therapeutic Plasma Exchange: Prescription Dosage, Timing, and Drug Overdose

“…Fauvelle et al. (45) found no correlation between PE clearance and the two main PK parameters responsible for TPE ability to remove drugs: protein binding and V d . In practical terms, observed decreases in serum concentrations during TPE (and attendant clearance/elimination constant calculations) do not reflect true amount eliminated after the procedure, because redistribution from tissues and the intravascular compartment often occurs after TPE completion (10) In addition, serum concentrations decline faster during TPE than tissue levels (10).…”