Pharmacokinetic aspects of interferon alfa-2b after intrahepatic or intraperitoneal administration.
The pharmacokinetics of interferon alfa-2b (IFN-alpha-2b) were determined following intraperitoneal (IP) infusion of escalating doses, ie, 5, 10, and 15 million units (MU) and intrahepatal-intraarterial (IA) (IA, bolus v 24 hours continuous infusion of 3 and 5 MU) administration in patients with metastatic cancer. Pharmacokinetic parameters show that bioavailability of IFN-alpha-2b after IP administration is 30 times higher for the peritoneal fluid (PF) than for peripheral blood (PB) explaining also the low incidence of side effects. The high affinity of IFN-alpha-2b to the peritoneal cavity is furthermore substantiated by the total compartment clearance, which is only about 1 1/minute for the PF in comparison to about 30 1/minute as determined for PB. IFN-alpha-2b is eliminated from the PF with a half life (t1/2) of elimination 10 to 32 hours and from the blood with t1/2 of 5 to 13 hours. After IA bolus, IFN is distributed from the blood with a t1/2 below, 2 hours, with dose-dependent serum peak concentrations (c = 47 IU for 3 MU and 145 IU for 5 MU). Twenty-four-hour infusion leads to a steady state within 4 to 6 hours and maximum concentration of 8.5 or 12.5 IU/mL, respectively. During infusion IFN alpha-2b is slowly eliminated with a t1/2 of 16 hours. The lower area under the curve levels after bolus injection may suggest a better tissue uptake of IFN-alpha-2b by the liver. Further studies on pharmacokinetics are warranted to establish exact dose recommendations for an optimal schedule using this route and mode of IFN-alpha-2b administration in mono- and combination therapies.
Schüller
J
J
First Medical Department, Hospital Rudolfstiftung, Vienna, Austria.
Czejka
M J
MJ
Schernthaner
G
G
Wirth
M
M
Bosse
C
C
Jäger
W
W
Micksche
M
M
D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D007263:Infusions, Parenteral; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000628:therapy; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins