Pharmacokinetics of ceftriaxone during plasma exchange in polyarteritis nodosa patients

Abstract

Plasma exchange (PE) is currently being used to treat a variety of disorders involving immune complexes, such as polyarteritis nodosa. This procedure removes endogenous toxic components that accumulate in patients with this disease, but it also removes drugs. Plasma-protein binding and the volume of distribution (V) are two kinetic parameters which strongly affect the efficiency of drug removal by PE. Drugs that are highly bound to plasma proteins and have a low V may show a marked decrease in plasma levels as a result of PE. Because ceftriaxone exhibits saturable plasma-protein binding, which influences its pharmacokinetic parameters, particularly its V, we evaluated its removal during PE therapy in this nonrandomized crossover study. 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. The mean amounts eliminated +/- standard deviations were 230.8 +/- 38.5 mg (1 g) and 750.0 +/- 168.5 mg (3 g) for group I and 161.0 +/- 66.0 mg (1 g) and 347.0 +/- 121.0 mg (3 g) for group II. The drug fractions eliminated by PE were 23.0% +/- 3.9% (1-g dose) and 24.9% +/- 5.6% (3-g dose) for group I (P > 0.05), and 16.6% +/- 5.9% (1-g dose) and 11.5% +/- 4.0% (3-g dose) for group II (P < 0.05). These results showed that the drug fraction eliminated decreased when V increased only when the distribution phase of ceftriaxone had been completed (group II). These findings suggest that PE may influence ceftriaxone disposition and that it would be better to administer the drug after PE to assure its therapeutic efficacy.

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

“…(13) advocated this parameter as the one with the most influence on compounds’ removal, taking precedence over protein binding and V d . This was supported by investigations noting an increased amount of drug removed when TPE was started immediately (teiclopenin [19], ceftriaxone [20]) or shortly (ceftazidime [21], phenobarbital [22]) after dose administration. Clinical observations corroborate these findings.…”

A novel way to investigate the effects of plasma exchange on antibiotic levels: use of microdialysis

“…Other studies on ␤-lactam antibiotics indicate that protein binding of the antibiotic is the important factor determining antibiotic removal. The third-generation cephalosporin ceftriaxone has a low V d and high protein binding and has been shown to be significantly removed by PE [19,20], whereas ceftazidime, another third-generation cephalosporin that has a low V d but low protein binding, has been shown not to be significantly affected by PE [21]. Given the data from this case, continuous infusion of ␤-lactam antibiotics should be encouraged in hospitalised patients receiving PE.…”

Pharmacokinetics of teicoplanin during plasma exchange

“…To ensure anticoagulation, citrate (pH 5.0±0.5) was given in a 1:10 v/v ratio with blood. Citrate has no effect on the protein binding of drugs [5]. Every patient underwent 14 sessions of plasma exchange over 3 weeks, and hemostasis was assessed before and after each session.…”

“…whereas Prince et al [3] reported a 35% decrease in plasma concentration of gentamicin compared to the initial level in newborns. β‐lactam elimination during plasma exchange has been the subject of four investigations: Prince et al [3] found that circulating ampicillin concentrations dropped by 35%; Bozkurt et al [1] noted that ceftazidime elimination varied from 2% to 9% depending on whether the patient had renal insufficiency; and Bakken et al [4] and Fauvelle et al [5] observed that the fraction of ceftriaxone eliminated reached 6–12% and 11.5–24% respectively, depending upon the time lapse between drug administration and the onset of plasma exchange. The influence of plasma exchange on the elimination of glycopeptides is unknown.…”