Pharmacokinetics of novel erythropoiesis stimulating protein (NESP) in cancer patients: preliminary report.
Anaemia is a common occurrence in patients with cancer, and currently can be treated in several ways. Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa) was created using site-directed mutagenesis to have 8 more sialic acid side chains than recombinant human erythropoietin (rHuEPO). The additional sialic acid content has resulted in an approximately 3-fold greater half-life relative to rHuEPO in patients with chronic renal failure. This study evaluates the pharmacokinetic profile of NESP in patients receiving multiple cycles of chemotherapy. Anaemic patients (haemoglobin < or = 11.0 g dl(-1)) who had non-myeloid malignancies received NESP weekly (2.25 mcg kg(-1) wk(-1)) under the supervision of a physician, starting on day 1 of chemotherapy for 3 chemotherapy cycles given at 3-week intervals. Blood samples were collected during chemotherapy cycles 1 and 3 for pharmacokinetic analysis. All patients were followed for 4 weeks after treatment. NESP was well tolerated by all patients. After a single dose during chemotherapy cycle 1, pharmacokinetic parameters (mean (SD), n) for the first 15 patients were: T(max)86.1 (22.8) h (n = 14); C(max)9.0 (5.1) ng ml(-1)(n = 14); t(1/2,z)32.6 (11.8) h (n = 7); CL/F 3.7 (1.0) ml h(-1) kg(-1)(n = 7). The subjects for whom all parameters could be calculated may represent a sub-group of the entire population. Similar results were obtained in cycle 3. In addition, haemoglobin response data suggests that, in this patient population, dosing less frequently than the 3 times weekly doses used for rHuEPO may be possible while improving anaemia.
Heatherington
A C
AC
Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
Schuller
J
J
Mercer
A J
AJ
D000328:Adult; D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068256:Darbepoetin alfa; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D012449:Safety
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D019158:N-Acetylneuraminic Acid