Plasma exchange and interferon-alpha pharmacokinetics in patients with hepatitis C virus-associated systemic vasculitis.
Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE.


METHODS
We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE.


RESULTS
Without PE, IFN C(max )(range: 100-750 IU/ml) was obtained 3-6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-alpha area under the curve decreased from 3,005 IU x h/ml (1,563-4,614) on days without PE to 2,142 IU x h/ml (973-4,123) on day with PE.


CONCLUSIONS
In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-alpha and PE therapy schedule have to be further studied to optimize its biological activity.
Hausfater
P
P
Department of Internal Medicine, CHU Pitié-Salpêtrière, Paris, France. pierre.hausfater@psl.ap-hop-paris.fr
Cacoub
P
P
Assogba
U
U
Lebon
P
P
Piette
J C
JC
D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D014657:Vasculitis / Q000150:complications / Q000628:therapy*
D016898:Interferon-alpha